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1.
Nat Genet ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38839885

RESUMO

Aneuploidy is frequently detected in early human embryos as a major cause of early pregnancy failure. However, how aneuploidy affects cellular function remains elusive. Here, we profiled the transcriptomes of 14,908 single cells from 203 human euploid and aneuploid blastocysts involving autosomal and sex chromosomes. Nearly all of the blastocysts contained four lineages. In aneuploid chromosomes, 19.5% ± 1.2% of the expressed genes showed a dosage effect, and 90 dosage-sensitive domains were identified. Aneuploidy leads to prevalent genome-wide transcriptome alterations. Common effects, including apoptosis, were identified, especially in monosomies, partially explaining the lower cell numbers in autosomal monosomies. We further identified lineage-specific effects causing unstable epiblast development in aneuploidies, which was accompanied by the downregulation of TGF-ß and FGF signaling, which resulted in insufficient trophectoderm maturation. Our work provides crucial insights into the molecular basis of human aneuploid blastocysts and may shed light on the cellular interaction during blastocyst development.

2.
BMC Musculoskelet Disord ; 25(1): 428, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824518

RESUMO

OBJECTIVE: To develop an AI-assisted MRI model to identify surgical target areas in pediatric hip and periarticular infections. METHODS: A retrospective study was conducted on the pediatric patients with hip and periarticular infections who underwent Magnetic Resonance Imaging(MRI)examinations from January 2010 to January 2023 in three hospitals in China. A total of 7970 axial Short Tau Inversion Recovery (STIR) images were selected, and the corresponding regions of osteomyelitis (label 1) and abscess (label 2) were labeled using the Labelme software. The images were randomly divided into training group, validation group, and test group at a ratio of 7:2:1. A Mask R-CNN model was constructed and optimized, and the performance of identifying label 1 and label 2 was evaluated using receiver operating characteristic (ROC) curves. Calculation of the average time it took for the model and specialists to process an image in the test group. Comparison of the accuracy of the model in the interpretation of MRI images with four orthopaedic surgeons, with statistical significance set at P < 0.05. RESULTS: A total of 275 patients were enrolled, comprising 197 males and 78 females, with an average age of 7.10 ± 3.59 years, ranging from 0.00 to 14.00 years. The area under curve (AUC), accuracy, sensitivity, specificity, precision, and F1 score for the model to identify label 1 were 0.810, 0.976, 0.995, 0.969, 0.922, and 0.957, respectively. The AUC, accuracy, sensitivity, specificity, precision, and F1 score for the model to identify label 2 were 0.890, 0.957, 0.969, 0.915, 0.976, and 0.972, respectively. The model demonstrated a significant speed advantage, taking only 0.2 s to process an image compared to average 10 s required by the specialists. The model identified osteomyelitis with an accuracy of 0.976 and abscess with an accuracy of 0.957, both statistically better than the four orthopaedic surgeons, P < 0.05. CONCLUSION: The Mask R-CNN model is reliable for identifying surgical target areas in pediatric hip and periarticular infections, offering a more convenient and rapid option. It can assist unexperienced physicians in pre-treatment assessments, reducing the risk of missed and misdiagnosis.


Assuntos
Imageamento por Ressonância Magnética , Osteomielite , Humanos , Masculino , Feminino , Imageamento por Ressonância Magnética/métodos , Criança , Estudos Retrospectivos , Adolescente , Osteomielite/diagnóstico por imagem , Pré-Escolar , Lactente , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/cirurgia , Articulação do Quadril/patologia , China , Abscesso/diagnóstico por imagem , Abscesso/cirurgia , Curva ROC
3.
Acad Radiol ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38871552

RESUMO

RATIONALE AND OBJECTIVES: to develop a deep learning radiomics graph network (DLRN) that integrates deep learning features extracted from gray scale ultrasonography, radiomics features and clinical features, for distinguishing parotid pleomorphic adenoma (PA) from adenolymphoma (AL) MATERIALS AND METHODS: A total of 287 patients (162 in training cohort, 70 in internal validation cohort and 55 in external validation cohort) from two centers with histologically confirmed PA or AL were enrolled. Deep transfer learning features and radiomics features extracted from gray scale ultrasound images were input to machine learning classifiers including logistic regression (LR), support vector machines (SVM), KNN, RandomForest (RF), ExtraTrees, XGBoost, LightGBM, and MLP to construct deep transfer learning radiomics (DTL) models and Rad models respectively. Deep learning radiomics (DLR) models were constructed by integrating the two features and DLR signatures were generated. Clinical features were further combined with the signatures to develop a DLRN model. The performance of these models was evaluated using receiver operating characteristic (ROC) curve analysis, calibration, decision curve analysis (DCA), and the Hosmer-Lemeshow test. RESULTS: In the internal validation cohort and external validation cohort, comparing to Clinic (AUC=0.767 and 0.777), Rad (AUC=0.841 and 0.748), DTL (AUC=0.740 and 0.825) and DLR (AUC=0.863 and 0.859), the DLRN model showed greatest discriminatory ability (AUC=0.908 and 0.908) showed optimal discriminatory ability. CONCLUSION: The DLRN model built based on gray scale ultrasonography significantly improved the diagnostic performance for benign salivary gland tumors. It can provide clinicians with a non-invasive and accurate diagnostic approach, which holds important clinical significance and value. Ensemble of multiple models helped alleviate overfitting on the small dataset compared to using Resnet50 alone.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38862429

RESUMO

DNA sequencers have become increasingly important research and diagnostic tools over the past 20 years. In this study, we developed a single-molecule desktop sequencer, GenoCare 1600 (GenoCare), which utilizes amplification-free library preparation and two-color sequencing-by-synthesis chemistry, making it more user-friendly compared with previous single-molecule sequencing platforms for clinical use. Using the GenoCare platform, we sequenced an Escherichia coli standard sample and achieved a consensus accuracy exceeding 99.99%. We also evaluated the sequencing performance of this platform in microbial mixtures and coronavirus disease 2019 (COVID-19) samples from throat swabs. Our findings indicate that the GenoCare platform allows for microbial quantitation, sensitive identification of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, and accurate detection of virus mutations, as confirmed by Sanger sequencing, demonstrating its remarkable potential in clinical application.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/virologia , COVID-19/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Análise de Sequência de DNA/métodos , Escherichia coli/genética , Mutação
5.
Sci Rep ; 14(1): 8532, 2024 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-38830912

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) poses challenges due to late-stage diagnosis and limited treatment response, often attributed to the hypoxic tumor microenvironment (TME). Sonoporation, combining ultrasound and microbubbles, holds promise for enhancing therapy. However, additional preclinical research utilizing commercially available ultrasound equipment for PDAC treatment while delving into the TME's intricacies is necessary. This study investigated the potential of using a clinically available ultrasound system and phase 2-proven microbubbles to relieve tumor hypoxia and enhance the efficacy of chemotherapy and immunotherapy in a murine PDAC model. This approach enables early PDAC detection and blood-flow-sensitive Power-Doppler sonoporation in combination with chemotherapy. It significantly extended treated mice's median survival compared to chemotherapy alone. Mechanistically, this combination therapy enhanced tumor perfusion and substantially reduced tumor hypoxia (77% and 67%, 1- and 3-days post-treatment). Additionally, cluster of differentiation 8 (CD8) T-cell infiltration increased four-fold afterward. The combined treatment demonstrated a strengthening of the anti-programmed death-ligand 1(αPDL1) therapy against PDAC. Our study illustrates the feasibility of using a clinically available ultrasound system with NH-002 microbubbles for early tumor detection, alleviating hypoxic TME, and improving chemotherapy and immunotherapy. It suggests the development of an adjuvant theragnostic protocol incorporating Power-Doppler sonoporation for pancreatic tumor treatment.


Assuntos
Carcinoma Ductal Pancreático , Imunoterapia , Microbolhas , Neoplasias Pancreáticas , Microambiente Tumoral , Animais , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Camundongos , Imunoterapia/métodos , Carcinoma Ductal Pancreático/terapia , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/patologia , Microambiente Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral , Hipóxia Tumoral/efeitos dos fármacos , Terapia Combinada , Humanos , Feminino
6.
Dig Dis Sci ; 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824258

RESUMO

BACKGROUND: In many Asian hepatocellular carcinoma (HCC) guidelines, resection is an option for multiple HCCs. It is difficult to compare small but multiple tumors vs. fewer large tumors in terms of the traditional tumor burden definition. We aimed to evaluate the role of liver resection for multiple HCCs and determine factors associated with survival benefits. METHODS: We reviewed 160 patients with multiple HCCs who underwent liver resection between July 2003 and December 2018. The risk factors for tumor recurrence were assessed using Cox proportional hazards modeling, and survival was analyzed using the Kaplan-Meier method. RESULTS: In all 160 patients, 133 (83.1%) exceeded the Milan criteria. Total tumor volume (TTV) > 275 cm3 and serum alpha-fetoprotein (AFP) level > 20 ng/mL were associated with disease-free survival. Patients beyond the Milan criteria were grouped into three risk categories: no risk (TTV ≤ 275 cm3 and AFP ≤ 20 ng/mL, n = 39), one risk (either TTV > 275 cm3 or AFP > 20 ng/mL, n = 76), and two risks (TTV > 275 cm3 and AFP > 20 ng/mL, n = 18). No-risk group had comparable disease-free survival (p = 0.269) and overall survival (p = 0.215) to patients who met the Milan criteria. CONCLUSION: Patients with TTV ≤ 275 cm3 and AFP ≤ 20 ng/mL can have good outcomes even exceed the Milan criteria.

7.
Cancer Lett ; : 217070, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38880227

RESUMO

The androgen receptor signaling inhibitor (ARSI) enzalutamide (Enz) has shown critical efficacy in the treatment of advanced prostate cancer (PCa). However, the development of drug resistance is a significant factor contributing to mortality in PCa patients. We aimed to explore the key mechanisms of Enz-resistance. Through analysis of GEO databases, we identified SLC4A4 as a novel driver in Enz resistance. Long-term Enz treatment leads to the up-regulation of SLC4A4, which in turn mediates P53 lactylation via the NF-κB/STAT3/SLC4A4 axis, ultimately leading to the development of Enz resistance and progression of PCa. SLC4A4 knockdown overcomes Enz resistance both in vitro and in vivo. Hence, our results suggest that targeting SLC4A4 could be a promising therapeutic strategy for Enz resistance. STATEMENT OF SIGNIFICANCE: SLC4A4 is a novel driver of enzalutamide resistance.

8.
Pathol Res Pract ; 260: 155372, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38878664

RESUMO

OBJECTIVE: To explore the clinical, imaging, pathologic characteristics and differential diagnosis of solitary pulmonary capillary hemangioma (SPCH). METHODS: Thirty two cases of SPCH were collected and studied, with literature review. RESULTS: This study included 13 males and 19 females, with a male-to-female ratio of 1:1.5. The age ranged from 26 to 70 years (median age of 43 years). All patients were asymptomatic at presentation. Lung nodules were incidentally discovered during chest computed tomography (CT). Imaging features included 21 cases with partial solid nodules (PSN), 7 cases with ground-glass nodules (GGN), and 4 cases with solid nodules (SN). Eleven cases were in the left lung lower basal segment, 11 cases in the right lung lower basal segment, 6 cases in the right lung upper anterior segment, and 4 cases in the right lung middle lateral segment. The lower basal segments of the lungs were involved in 22 (11 in each lung) cases (22/32, 68 %). The tumors ranged from 6 to 18 mm (average 10 mm). Macroscopically, 16 cases had clear boundaries, while 16 cases had unclear boundaries, and gray-red or dark brown on cut surfaces. Intraoperative frozen section was performed in 27 cases, with diagnosis of SPCH in 12 and pneumonia or inflammatory lesion in 15. Microscopically, the nodules were composed of densely proliferated and dilated capillaries. The capillary walls were lined with a single layer of flat endothelial cells, without atypical features. Collapsed alveolar septa were replaced by a large number of capillaries. All cases showed proliferating capillaries spreading into the walls of small veins/arteries and bronchi, with 3 cases showing dilated capillaries protruding into the bronchiolar lumens as polyp-like structures. Twenty-six cases (26/32, 81 %) showed proliferating capillaries passed over the interlobular septa. Twenty-six cases (26/32, 81 %) showed irregular intimal thickening of small muscular arteries in the peripheral areas of the lesions, with the thickened intima being cellular or fibrous. In twenty-seven cases (27/32, 84 %) the lesions were located in the subpleura, with 6 cases involving the pleura. CONCLUSION: SPCH is a rare benign lung tumor that mostly occurs in the lung lower basal segments with predominance in females. It usually appears as a ground-glass nodule on CT and is very similar to early-stage lung cancer. Accurate diagnosis requires collaboration of radiologists, surgeons, and pathologists. SPCH should be regarded as an important differential diagnosis of small incidental lung nodules.

10.
Skin Res Technol ; 30(6): e13791, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38895902

RESUMO

BACKGROUND: Hypertrophic scars (HS) are a common disfiguring condition in daily clinical encounters which brings a lot of anxieties and concerns to patients, but the treatment options of HS are limited. Black cloth ointment (BCO), as a cosmetic ointment applicable to facial scars, has shown promising therapeutic effects for facial scarring. However, the molecular mechanisms underlying its therapeutic effects remain unclear. MATERIAL AND METHODS: Network pharmacology was first applied to analyze the major active components of BCO and the related signaling pathways. Subsequently, rabbit ear scar model was successfully established to determine the pharmacological effects of BCO and its active component ß-elemene on HS. Finally, the molecular mechanism of BCO and ß-elemene was analyzed by Western blot. RESULTS: Through the network pharmacology, it showed that ß-elemene was the main active ingredient of BCO, and it could significantly improve the pathological structure of HS and reduce collagen deposition. BCO and ß-elemene could increase the expression of ER stress-related markers and promote the increase of apoptotic proteins in the Western blot experiment and induce the apoptosis of myofibroblasts. CONCLUSIONS: Our findings indicate that the material basis for the scar-improving effects of the BCO is ß-elemene, and cellular apoptosis is the key mechanism through which the BCO and ß-elemene exert their effects.


Assuntos
Cicatriz Hipertrófica , Modelos Animais de Doenças , Farmacologia em Rede , Pomadas , Sesquiterpenos , Cicatriz Hipertrófica/tratamento farmacológico , Cicatriz Hipertrófica/patologia , Cicatriz Hipertrófica/metabolismo , Coelhos , Animais , Farmacologia em Rede/métodos , Sesquiterpenos/farmacologia , Humanos , Apoptose/efeitos dos fármacos , Feminino , Masculino
11.
BMC Ophthalmol ; 24(1): 236, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844881

RESUMO

BACKGROUND: Ocular tuberculosis is a relatively rare extrapulmonary manifestation of tuberculosis. This vision-threatening disease is extremely challenging to diagnose, particularly because it can mimic other diseases. We report a case of tuberculous ciliary body granuloma initially diagnosed as bullous retinal detachment. CASE REPORT: A 52-year-old female presented with bullous retinal detachment in her left eye, and ultrasound biomicroscopy (UBM) verified the presence of a lesion with ciliary body granulomatous inflammation. The T-SPOT was positive, and the purified protein derivative (PPD) test was strongly positive (diameter of 20 mm). Following the administration of oral anti-tuberculosis regimen combined with prednisone, the retina gradually became reattached, the ciliary body granuloma became significantly reduced in size, and the visual acuity of the patient noticeably improved. CONCLUSIONS: Tuberculous ciliary body granulomas can cause bullous exudative retinal detachment and can be diagnosed with UBM. Early and full-course anti-tuberculosis treatment (ATT) combined with corticosteroid therapy can improve the patient prognosis.


Assuntos
Corpo Ciliar , Descolamento Retiniano , Tuberculose Ocular , Humanos , Feminino , Pessoa de Meia-Idade , Tuberculose Ocular/diagnóstico , Tuberculose Ocular/tratamento farmacológico , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/etiologia , Corpo Ciliar/patologia , Granuloma/diagnóstico , Doenças da Úvea/diagnóstico , Diagnóstico Diferencial , Microscopia Acústica , Antituberculosos/uso terapêutico
12.
Front Pharmacol ; 15: 1380098, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38881875

RESUMO

Rheumatoid arthritis is a chronic immunological disease leading to the progressive bone and joint destruction. Angiogenesis, accompanied by synovial hyperplasia and inflammation underlies joint destruction. Delaying or even blocking synovial angiogenesis has emerged as an important target of RA treatment. Natural medicines has a long history of treating RA, and numerous reports have suggested that natural medicines have a strong inhibitory activity on synovial angiogenesis, thereby improving the progression of RA. Natural medicines could regulate the following signaling pathways: HIF/VEGF/ANG, PI3K/Akt pathway, MAPKs pathway, NF-κB pathway, PPARγ pathway, JAK2/STAT3 pathway, etc., thereby inhibiting angiogenesis. Tripterygium wilfordii Hook. f. (TwHF), sinomenine, and total glucoside of Paeonia lactiflora Pall. Are currently the most representative of all natural products worthy of development and utilization. In this paper, the main factors affecting angiogenesis were discussed and different types of natural medicines that inhibit angiogenesis were systematically summarized. Their specific anti-angiogenesis mechanisms are also reviewed which aiming to provide new perspective and options for the management of RA by targeting angiogenesis.

13.
Adv Mater ; : e2404968, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38897182

RESUMO

Color-selective photodetectors (PDs) play an indispensable role in spectral recognition, image sensing and other fields. Nevertheless, complex filters and delicate optical paths in such devices significantly increase their complexity and size, which subsequently impede their integration in smart optoelectronic chips for universal applications. This work demonstrates the successful fabrication of filter-less color-selective perovskite PDs by integrating three perovskite units with different photo response on a single chip. The variation in photo response is attributed to different quantities of SnO2 nanoparticles, synthesized through controlled ultrasonic treatment on the surface of the electron transportation layer SnS2, which selectively absorb short-wavelength light, thus increasing the relative transmittance of long-wavelength light and enhancing the photo response of the units to long wavelengths. By integrating any two units and deriving the formula for the wavelength to the responsivity ratio, a wavelength sensor is developed which can accurately identify incident light in the range of 400-700 nm with a minimum error <3 nm. Furthermore, the device integrating three units with different photo response can identify red, green, and blue in polychromatic light to achieve color imaging with a relative error <6%. This work provides valuable insights into wavelength identification and color imaging of perovskite PDs. This article is protected by copyright. All rights reserved.

14.
Anal Chem ; 96(21): 8325-8331, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38738931

RESUMO

The high expression of Spermidine/spermine N1-acetyltransferase (SSAT-1) is an important indicator in early cancer diagnosis. Here, we developed a nanopore-based methodology with γ-cyclodextrin as an adaptor to detect and quantify acetylamantadine, the specific SSAT-1-catalyzed product from amantadine, to accordingly reflect the activity of SSAT-1. We employ γ-cyclodextrin and report that amantadine cannot cause any secondary signals in γ-cyclodextrin-assisted α-HL nanopore, while its acetylation product, acetylamantadine, does. This allows γ-cyclodextrin to practically detect acetylamantadine in the interference of excessive amantadine, superior to the previously reported ß-cyclodextrin. The quantification of acetylamantadine was not interfered with even a 50-fold amantadine and displayed no interference in artificial urine sample analysis, which indicates the good feasibility of this nanopore-based methodology in painless cancer prediagnosis. In addition, the discrimination mechanism is also explored by 2-D nuclear magnetic resonance (NMR) and nanopore experiments with a series of adamantane derivatives with different hydrophilic and hydrophobic groups. We found that both the hydrophobic region matching effect and hydrophilic interactions play a synergistic effect in forming a host-guest complex to further generate the characteristic signals, which may provide insights for the subsequent design and study of drug-cyclodextrin complexes.


Assuntos
Amantadina , Nanoporos , gama-Ciclodextrinas , gama-Ciclodextrinas/química , Humanos , Amantadina/química , Amantadina/análise , Neoplasias
15.
IEEE Trans Med Imaging ; PP2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38801692

RESUMO

Dynamic contrast-enhanced ultrasound (CEUS) imaging can reflect the microvascular distribution and blood flow perfusion, thereby holding clinical significance in distinguishing between malignant and benign thyroid nodules. Notably, CEUS offers a meticulous visualization of the microvascular distribution surrounding the nodule, leading to an apparent increase in tumor size compared to gray-scale ultrasound (US). In the dual-image obtained, the lesion size enlarged from gray-scale US to CEUS, as the microvascular appeared to be continuously infiltrating the surrounding tissue. Although the infiltrative dilatation of microvasculature remains ambiguous, sonographers believe it may promote the diagnosis of thyroid nodules. We propose a deep learning model designed to emulate the diagnostic reasoning process employed by sonographers. This model integrates the observation of microvascular infiltration on dynamic CEUS, leveraging the additional insights provided by gray-scale US for enhanced diagnostic support. Specifically, temporal projection attention is implemented on time dimension of dynamic CEUS to represent the microvascular perfusion. Additionally, we employ a group of confidence maps with flexible Sigmoid Alpha Functions to aware and describe the infiltrative dilatation process. Moreover, a self-adaptive integration mechanism is introduced to dynamically integrate the assisted gray-scale US and the confidence maps of CEUS for individual patients, ensuring a trustworthy diagnosis of thyroid nodules. In this retrospective study, we collected a thyroid nodule dataset of 282 CEUS videos. The method achieves a superior diagnostic accuracy and sensitivity of 89.52% and 93.75%, respectively. These results suggest that imitating the diagnostic thinking of sonographers, encompassing dynamic microvascular perfusion and infiltrative expansion, proves beneficial for CEUS-based thyroid nodule diagnosis.

16.
Am J Manag Care ; 30(6 Spec No.): SP430-SP436, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38820183

RESUMO

OBJECTIVES: This study simulated the potential multiyear health and economic benefits of participation in 4 cardiometabolic virtual-first care (V1C) programs: prevention, hypertension, diabetes, and diabetes plus hypertension. STUDY DESIGN: Using nationally available data and existing clinical and demographic information from members participating in cardiometabolic V1C programs, a microsimulation approach was used to estimate potential reduction in onset of disease sequelae and associated gross savings (ie, excluding the cost of V1C programs) in health care costs. METHODS: Members of each program were propensity matched to similar records in the combined 2012-2020 National Health and Nutrition Examination Survey files based on age, sex, race/ethnicity, body mass index, and diagnosis status of diabetes and/or hypertension. V1C program-attributed changes in clinical outcomes combined with baseline biometric levels and other risk factors were used as inputs to model disease onset and related gross health care costs. RESULTS: Across the V1C programs, sustained improvements in weight loss, hemoglobin A1c, and blood pressure levels were estimated to reduce incidence of modeled disease sequelae by 2% to 10% over the 5 years following enrollment. As a result of sustained improvement in biometrics and reduced disease onset, the estimated gross savings in medical expenditures across the programs would be $892 to $1342 after 1 year, and cumulative estimated gross medical savings would be $2963 to $4346 after 3 years and $5221 to $7756 after 5 years. In addition, high program engagement was associated with greater health and economic benefits. CONCLUSIONS: V1C programs for prevention and management of cardiometabolic chronic conditions have potential long-term health and financial implications.


Assuntos
Hipertensão , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Análise Custo-Benefício , Adulto , Estados Unidos , Modelos Econômicos , Inquéritos Nutricionais , Diabetes Mellitus/prevenção & controle , Diabetes Mellitus/economia , Diabetes Mellitus/terapia , Custos de Cuidados de Saúde/estatística & dados numéricos , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/economia
17.
Cell Commun Signal ; 22(1): 292, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802843

RESUMO

BACKGROUND: Hematopoietic stem cell (HSC) regeneration underlies hematopoietic recovery from myelosuppression, which is a life-threatening side effect of cytotoxicity. HSC niche is profoundly disrupted after myelosuppressive injury, while if and how the niche is reshaped and regulates HSC regeneration are poorly understood. METHODS: A mouse model of radiation injury-induced myelosuppression was built by exposing mice to a sublethal dose of ionizing radiation. The dynamic changes in the number, distribution and functionality of HSCs and megakaryocytes were determined by flow cytometry, immunofluorescence, colony assay and bone marrow transplantation, in combination with transcriptomic analysis. The communication between HSCs and megakaryocytes was determined using a coculture system and adoptive transfer. The signaling mechanism was investigated both in vivo and in vitro, and was consolidated using megakaryocyte-specific knockout mice and transgenic mice. RESULTS: Megakaryocytes become a predominant component of HSC niche and localize closer to HSCs after radiation injury. Meanwhile, transient insulin-like growth factor 1 (IGF1) hypersecretion is predominantly provoked in megakaryocytes after radiation injury, whereas HSCs regenerate paralleling megakaryocytic IGF1 hypersecretion. Mechanistically, HSCs are particularly susceptible to megakaryocytic IGF1 hypersecretion, and mTOR downstream of IGF1 signaling not only promotes activation including proliferation and mitochondrial oxidative metabolism of HSCs, but also inhibits ferritinophagy to restrict HSC ferroptosis. Consequently, the delicate coordination between proliferation, mitochondrial oxidative metabolism and ferroptosis ensures functional HSC expansion after radiation injury. Importantly, punctual IGF1 administration simultaneously promotes HSC regeneration and hematopoietic recovery after radiation injury, representing a superior therapeutic approach for myelosuppression. CONCLUSIONS: Our study identifies megakaryocytes as a last line of defense against myelosuppressive injury and megakaryocytic IGF1 as a novel niche signal safeguarding HSC regeneration.


Assuntos
Ferroptose , Células-Tronco Hematopoéticas , Fator de Crescimento Insulin-Like I , Megacariócitos , Regeneração , Animais , Células-Tronco Hematopoéticas/metabolismo , Megacariócitos/metabolismo , Megacariócitos/efeitos da radiação , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like I/genética , Ferroptose/genética , Camundongos , Camundongos Endogâmicos C57BL , Lesões por Radiação/metabolismo , Lesões por Radiação/patologia , Lesões por Radiação/genética , Transdução de Sinais/efeitos da radiação
18.
Phys Chem Chem Phys ; 26(22): 16096-16106, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38780318

RESUMO

In this study, we proposed a bifunctional sensor of high sensitivity and slow light based on carbon nanotubes (CNTs). An array of left semicircular ring (LSR), right semicircular ring (RSR), and circular ring (CR) resonators are utilized to form the proposed metamaterial. The proposed structure can achieve double plasmon-induced transparency (PIT) effects under the excitation of a TM-polarization wave. The double PIT originated from the destructive interference between two bright modes and a dark mode. A coupled harmonic oscillator model is used to describe the destructive interference between the two bright modes and a dark mode, and the simulation results agree well with the calculated results. Moreover, we investigate the influence of the coupling distance, period, and flare angle on the PIT spectra. The relationship between the resonant frequencies, full width at half maximum (FWHM), amplitudes, quality factors (Q), and the coupling distance is also studied. Finally, a high sensitivity of 1.02 THz RIU-1 is obtained, and the transmission performance can be maintained at a good level when the incident angle is less than 40°. Thus, the sensor can cope with situations where electromagnetic waves are not perpendicular to the structure's surface. The maximum figure of merit (FOM) can reach about 8.26 RIU-1; to verify the slow light property of the device, the slow light performance of the proposed structure is investigated, and a maximum time delay (TD) of 22.26 ps is obtained. The proposed CNT-based metamaterial can be used in electromagnetically induced transparency applications, such as sensors, optical memory devices, and flexible terahertz functional devices.

19.
Discov Nano ; 19(1): 94, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38806816

RESUMO

In this research, we introduce an advanced methodology for the calculation of bulk light sources tailored for free-form surface design, focusing on the principle of energy conservation. This method is especially relevant for the evolving needs of micro-LED packaging, highlighting its potential in this burgeoning field. Our work includes the development of an algorithm for creating freeform-designed chip-scale package (FDCSP) components. These components seamlessly integrate LEDs and lenses, underscoring our commitment to advancing free-form surface design in chip-level packaging. By adhering to the principle of energy conservation, our approach facilitates a meticulous comparison of simulation outcomes with predefined target functions. This enables the iterative correction of discrepancies, employing layering techniques to refine the design until the simulated results closely align with our goals, as demonstrated by an appropriate difference curve. The practical application of these simulations leads to the innovative design of FDCSP devices. Notably, these devices are not just suitable for traditional applications in backlight modules but are explicitly optimized for the emerging sector of micro-LED packaging. Our successful demonstration of these FDCSP devices within backlight modules represents a significant achievement. It underscores the effectiveness of our design strategy and its expansive potential to transform micro-LED packaging solutions. This research not only contributes to the theoretical understanding of energy conservation in lighting design but also paves the way for groundbreaking applications in micro-LED and backlight module technologies.

20.
MedComm (2020) ; 5(6): e560, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38812572

RESUMO

White adipose tissue is not only a highly heterogeneous organ containing various cells, such as adipocytes, adipose stem and progenitor cells, and immune cells, but also an endocrine organ that is highly important for regulating metabolic and immune homeostasis. In individuals with obesity, dynamic cellular changes in adipose tissue result in phenotypic switching and adipose tissue dysfunction, including pathological expansion, WAT fibrosis, immune cell infiltration, endoplasmic reticulum stress, and ectopic lipid accumulation, ultimately leading to chronic low-grade inflammation and insulin resistance. Recently, many distinct subpopulations of adipose tissue have been identified, providing new insights into the potential mechanisms of adipose dysfunction in individuals with obesity. Therefore, targeting white adipose tissue as a therapeutic agent for treating obesity and obesity-related metabolic diseases is of great scientific interest. Here, we provide an overview of white adipose tissue remodeling in individuals with obesity including cellular changes and discuss the underlying regulatory mechanisms of white adipose tissue metabolic dysfunction. Currently, various studies have uncovered promising targets and strategies for obesity treatment. We also outline the potential therapeutic signaling pathways of targeting adipose tissue and summarize existing therapeutic strategies for antiobesity treatment including pharmacological approaches, lifestyle interventions, and novel therapies.

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