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1.
Nature ; 613(7945): 667-675, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36697864

RESUMEN

Continuous imaging of cardiac functions is highly desirable for the assessment of long-term cardiovascular health, detection of acute cardiac dysfunction and clinical management of critically ill or surgical patients1-4. However, conventional non-invasive approaches to image the cardiac function cannot provide continuous measurements owing to device bulkiness5-11, and existing wearable cardiac devices can only capture signals on the skin12-16. Here we report a wearable ultrasonic device for continuous, real-time and direct cardiac function assessment. We introduce innovations in device design and material fabrication that improve the mechanical coupling between the device and human skin, allowing the left ventricle to be examined from different views during motion. We also develop a deep learning model that automatically extracts the left ventricular volume from the continuous image recording, yielding waveforms of key cardiac performance indices such as stroke volume, cardiac output and ejection fraction. This technology enables dynamic wearable monitoring of cardiac performance with substantially improved accuracy in various environments.


Asunto(s)
Ecocardiografía , Diseño de Equipo , Corazón , Dispositivos Electrónicos Vestibles , Humanos , Gasto Cardíaco , Ecocardiografía/instrumentación , Ecocardiografía/normas , Corazón/diagnóstico por imagen , Ventrículos Cardíacos/diagnóstico por imagen , Volumen Sistólico , Dispositivos Electrónicos Vestibles/normas , Piel
2.
Opt Express ; 29(23): 37809-37819, 2021 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-34808846

RESUMEN

High-order harmonic generation in solid state has attracted a lot of attentions. The Berry curvature (BC), a geometrical property of the Bloch energy band, plays an important role for the harmonic generation in crystal. As we all know, the influence of BC on the harmonic emission has been investigated before and BC is simplified as a 1D structure. However, many other materials including MoS2 are 2D materials. In this work, we extend the investigation for BC to 2D structure and get a generalized equation, which not only gives a new method to control the harmonic emission with BC, but also gives a deeper understanding for the influence of the BC. We show the ability to control the harmonic emission related to the BC using the orthogonal two-color (OTC) laser field. By tuning the delay of OTC laser field, one can steer the trajectory of electrons and modulate the emission of harmonics. This study can provide us a deeper insight into the role of the BC which is difficult to be measured experimentally.

3.
Int J Mol Sci ; 22(15)2021 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-34361052

RESUMEN

Colon cancer (CC) is considered a high-risk cancer in developed countries. Its etiology is correlated with a high consumption of red meat and low consumption of plant-based foods, including whole grains. Sorghum bran is rich in polyphenols. This study aimed to determine whether different high-phenolic sorghum brans suppress tumor formation in a genetic CC rodent model and elucidate mechanisms. Tissue culture experiments used colorectal cancer cell lines SW480, HCT-116 and Caco-2 and measured protein expression, and protein activity. The animal model used in this study was APC Min+/mouse model combined with dextram sodium sulfate. High phenolic sorghum bran extract treatment resulted in the inhibition of proliferation and induced apoptosis in CC cell lines. Treatment with high phenolic sorghum bran extracts repressed TNF-α-stimulated NF-κB transactivation and IGF-1-stimulated PI3K/AKT pathway via the downregulation of ß-catenin transactivation. Furthermore, high-phenolic sorghum bran extracts activated AMPK and autophagy. Feeding with high-phenolic sorghum bran for 6 weeks significantly suppressed tumor formation in an APC Min/+ dextran sodium sulfate promoted CC mouse model. Our data demonstrates the potential application of high-phenolic sorghum bran as a functional food for the prevention of CC.


Asunto(s)
Proteína de la Poliposis Adenomatosa del Colon/fisiología , Neoplasias Colorrectales/tratamiento farmacológico , Sulfato de Dextran/toxicidad , Modelos Animales de Enfermedad , Extractos Vegetales/farmacología , Sorghum/química , Animales , Apoptosis , Proliferación Celular , Neoplasias Colorrectales/inducido químicamente , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Femenino , Humanos , Masculino , Ratones , Células Tumorales Cultivadas
4.
J Sci Food Agric ; 101(7): 2641-2649, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33179254

RESUMEN

Sorghum is one of the most widely cultivated crops, and is used in foods, domestic animal feedstuffs, alcohol production, and biofuels. Recently, many research groups have demonstrated that sorghum contains various components that are strongly associated with the prevention of major human chronic diseases such as obesity, diabetes, atherosclerosis, cancer, and inflammation. However, to use sorghum more widely as a food for the potential prevention and treatment of human chronic diseases, more studies will be required to elucidate the biological mechanisms. In this review paper, we highlight multiple findings to propose a mechanistic link between sorghum consumption and reduced risk of chronic diseases. © 2020 Society of Chemical Industry.


Asunto(s)
Enfermedad Crónica/prevención & control , Sorghum/metabolismo , Animales , Dietoterapia , Humanos , Sorghum/química
5.
Mol Carcinog ; 58(6): 922-932, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30676667

RESUMEN

Epithelial specific ETS-1 (ESE-1) belongs to the E26 transformation-specific transcription factor superfamily and is of great interest as a potential target for managing several types of cancer. Despite its clinical significance, the documented effects of ESE-1 on cancer development and progression are contradictory and its underlying biological mechanism of action remains elusive. The objectives of this study are to investigate whether ESE-1 is a tumor suppressor and to identify dietary anti-cancer compound to activate ESE-1 expression in human colon cancer model. ESE-1 knockout and xenograft mouse models were used to examine the effect of ESE-1 in colon tumorigenesis. Stable human colon cancer cell lines were used for in vitro mechanistic studies. ESE-1 knockout in mice increased azoxymethane (AOM)-induced and dextran sulfate sodium (DSS)-promoted formation of aberrant crypt foci (ACF). Conversely, overexpression of ESE-1 suppressed tumorigenicity in a xenograft mouse study, and repressed anchorage-independent growth and migration/invasion in human colon cancer cells. Full length ESE-1 localized abundantly in the nucleus, and internal deletion of nuclear localization sequence 2 (NLS2) reduced nuclear ESE-1. Three lysine residues (318 KKK320 ) in the NLS2 determine its nuclear localization. We identified epigallocatechin-3-gallate (EGCG) that acts as a transcriptional activator of ESE-1 in human colon cancer cells. These findings propose a novel and promising molecular target of dietary anti-cancer compounds for prevention of colon cancer.


Asunto(s)
Antineoplásicos Fitogénicos/administración & dosificación , Catequina/análogos & derivados , Neoplasias del Colon/tratamiento farmacológico , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Proteínas Proto-Oncogénicas c-ets/genética , Proteínas Proto-Oncogénicas c-ets/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Animales , Antineoplásicos Fitogénicos/farmacología , Azoximetano/efectos adversos , Células CACO-2 , Catequina/administración & dosificación , Catequina/farmacología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Neoplasias del Colon/inducido químicamente , Neoplasias del Colon/genética , Neoplasias del Colon/patología , Proteínas de Unión al ADN/química , Sulfato de Dextran/efectos adversos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Técnicas de Silenciamiento del Gen , Células HCT116 , Células HT29 , Humanos , Ratones , Señales de Localización Nuclear , Proteínas Proto-Oncogénicas c-ets/química , Factores de Transcripción/química , Ensayos Antitumor por Modelo de Xenoinjerto
6.
Biochem Biophys Res Commun ; 493(2): 934-939, 2017 11 18.
Artículo en Inglés | MEDLINE | ID: mdl-28951214

RESUMEN

Arctigenin (ARC) is a lignan that is abundant in Asteraceae plants, which show anti-inflammatory and anti-cancer activities. The current study investigated whether ARC affects cancer progression and metastasis, focusing on EMT using invasive human non-small cell lung cancer (NSCLC) cells. No toxicity was observed in the cells treated with different doses of ARC (12-100 µM). The treatment of ARC repressed TGF-ß-stimulated changes of metastatic morphology and cell invasion and migration. ARC inhibited TGF-ß-induced phosphorylation and transcriptional activity of smad2/3, and expression of snail. ARC also decreased expression of N-cadherin and increased expression of E-cadherin in dose-dependent and time-dependent manners. These changes were accompanied by decreased amount of phospho-smad2/3 in nucleus and nuclear translocation of smad2/3. Moreover, ARC repressed TGF-ß-induced phosphorylation of ERK and transcriptional activity of ß-catenin. Our data demonstrate anti-metastatic activity of ARC in lung cancer model.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Transición Epitelial-Mesenquimal/efectos de los fármacos , Furanos/farmacología , Lignanos/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Factor de Crecimiento Transformador beta/metabolismo , Antineoplásicos Fitogénicos/química , Asteraceae/química , Cadherinas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Furanos/química , Humanos , Lignanos/química , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Invasividad Neoplásica/patología , Invasividad Neoplásica/prevención & control , Fosforilación/efectos de los fármacos , Proteína Smad2/metabolismo , Proteína smad3/metabolismo , beta Catenina/metabolismo
7.
Artículo en Inglés | MEDLINE | ID: mdl-38905093

RESUMEN

Gestures are composed of motion information (e.g. movements of fingers) and force information (e.g. the force exerted on fingers when interacting with other objects). Current hand gesture recognition solutions such as cameras and strain sensors primarily focus on correlating hand gestures with motion information and force information is seldom addressed. Here we propose a bio-impedance wearable that can recognize hand gestures utilizing both motion information and force information. Compared with previous impedance-based gesture recognition devices that can only recognize a few multi-degrees-of-freedom gestures, the proposed device can recognize 6 single-degree-of-freedom gestures and 20 multiple-degrees-of-freedom gestures, including 8 gestures in 2 force levels. The device uses textile electrodes, is benchmarked over a selected frequency spectrum, and uses a new drive pattern. Experimental results show that 179 kHz achieves the highest signal-to-noise ratio (SNR) and reveals the most distinct features. By analyzing the 49,920 samples from 6 participants, the device is demonstrated to have an average recognition accuracy of 98.96%. As a comparison, the medical electrodes achieved an accuracy of 98.05%.

8.
Nat Biotechnol ; 42(3): 448-457, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37217752

RESUMEN

Recent advances in wearable ultrasound technologies have demonstrated the potential for hands-free data acquisition, but technical barriers remain as these probes require wire connections, can lose track of moving targets and create data-interpretation challenges. Here we report a fully integrated autonomous wearable ultrasonic-system-on-patch (USoP). A miniaturized flexible control circuit is designed to interface with an ultrasound transducer array for signal pre-conditioning and wireless data communication. Machine learning is used to track moving tissue targets and assist the data interpretation. We demonstrate that the USoP allows continuous tracking of physiological signals from tissues as deep as 164 mm. On mobile subjects, the USoP can continuously monitor physiological signals, including central blood pressure, heart rate and cardiac output, for as long as 12 h. This result enables continuous autonomous surveillance of deep tissue signals toward the internet-of-medical-things.


Asunto(s)
Dispositivos Electrónicos Vestibles , Humanos , Signos Vitales
9.
Tumour Biol ; 34(5): 2489-95, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23857285

RESUMEN

Published studies researching the prognostic significance of cyclooxygenase-2 (COX-2) expression in patients with osteosarcoma are inconclusive and heterogeneous. We conducted a meta-analysis to assess its prognostic value more precisely. The pooled odds ratios (ORs) or hazard ratios (HRs) with corresponding 95 % confidence intervals (CIs) were calculated to evaluate the effects. Fourteen studies with 735 osteosarcoma patients were included to estimate the relationship between COX-2 and metastasis of tumor, clinical stage, and 3-year overall survival. High expressions of COX-2 predicted neoplasm metastasis (OR = 1.891, 95 % CI 1.276-2.803, P = 0.002), advanced clinical stage (OR = 1.801, 95 % CI 1.257-2.581, P = 0.001). In addition, high COX-2 expression tended to be associated with a poor 3-year survival (HR = 1.741, 95 % CI 0.762-3.979, P = 0.188), but the difference was not significant. Therefore, this meta-analysis demonstrated that high COX-2 expression might be an unfavorable prognostic effect in osteosarcoma.


Asunto(s)
Neoplasias Óseas/enzimología , Ciclooxigenasa 2/metabolismo , Osteosarcoma/enzimología , Neoplasias Óseas/mortalidad , Neoplasias Óseas/patología , Humanos , Estimación de Kaplan-Meier , Estadificación de Neoplasias , Oportunidad Relativa , Osteosarcoma/mortalidad , Osteosarcoma/patología , Pronóstico
10.
Injury ; 54 Suppl 2: S36-S42, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35999065

RESUMEN

OBJECTIVES: To assess the medium-term functional and radiological outcomes, as well as injury mechanisms, fracture patterns and demographics of typical pilon fractures and pilon variant fractures treated based on the four-column theory in adults. METHODS: A retrospective comparative study was performed. Demographics of typical pilon and pilon variant fractures, injury mechanisms, OTA/AO classification, Rüedi-Allgöwer and the four-column classification were analyzed for the cohort. Radiographic ankle arthrosis (modified Kellgren-Lawrence 3/4), Burwell Charnley Score, and AOFAS score were also analyzed. RESULTS: There were 142 pilon fractures met the inclusion and exclusion criteria for this study, of which 77(54.23%) were females and 65 (45.77%) were males, with an average of 48 (range, 18-86)years. One hundred twenty-five posterior columns fractured in 142 pilon fractures, and the posterior columns were most prone to fractures. Ninety cases of posterior pilon fractures in 142 pilon fractures were single posterior column fractures with or without medial or lateral malleolar fractures. The average age (51, range, 18-86 years) of low-energy pilon fractures was older than the average age (42, range, 19-66 years) of high-energy pilon fractures significantly. The average time (5, range, 0-17 days) from injury to definitive internal fixation of the low-energy group was shorter than the average time (9, range, 0-21 days) from injury to definitive internal fixation of the high-energy group significantly. The average of AOFAS (87, range, 56-100) of the low-energy group is higher than the average of AOFAS (82, range, 47-100) of the high-energy group significantly. There were more male patients and more die-punch or intercalary fractures in high energy groups significantly. There were more medial and lateral malleolar fractures in low-energy groups. Compared with the non-multiple column group, the multiple-column group had more Rüedi-Allgöwer type III cases, more modified Kellgren-Lawrence 3/4 cases and lower AOFAS score significantly. However, the numbers of Burwell Charnley Score type 1 and 2 cases were not significantly different between the two groups. CONCLUSIONS: Kinds of pilon variants should be recognized. Outcomes of high-energy pilon fractures were worse than low-energy pilon fractures. The four-column theory can be applied to typical pilon fracture and pilon variants in adults.


Asunto(s)
Fracturas de Tobillo , Fracturas de la Tibia , Adulto , Femenino , Humanos , Masculino , Adolescente , Adulto Joven , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Estudios Retrospectivos , Fracturas de la Tibia/diagnóstico por imagen , Fracturas de la Tibia/cirugía , Tibia , Fracturas de Tobillo/diagnóstico por imagen , Fracturas de Tobillo/cirugía , Fijación Interna de Fracturas
11.
Financ Innov ; 9(1): 48, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36741237

RESUMEN

Despite blockchain's potential to transform corporations by providing new ways of organizing business processes and handling information, extant research pays inadequate attention to how and under what conditions blockchain technology provides additional financial value for shareholders. Drawing on the efficient market hypothesis and signaling theory, we examined the relationship between firms' blockchain use, development announcements, and stock market reactions. We used the event study methodology to analyze a sample of blockchain projects initiated by US firms between 2016 and 2019. The sample contains 114 firm-event observations. The findings show that the average abnormal return over a 2 days event period (including the day of the announcement and the day after the announcement) was positive. This positive stock market reaction is even more substantial when firms announce blockchain projects that focus on saving cost or time. Our findings also indicate that blockchain announcements tend to elicit more positive market reactions from smaller firms. We analyzed 249 firm-event observations containing firms from around the world and conclude that blockchain technology has a non-significant long-term impact on operating performance. The contingency approach adopted in our research provides advice for selecting the right mix of blockchain investment initiatives that is most suitable for a given organizational context.

12.
Front Med (Lausanne) ; 10: 1263930, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38179269

RESUMEN

Purpose: Contralateral hip refracture following initial hip fracture surgery is life-threatening in the elderly with high incidence and mortality. This study investigated the associated independent risk factors and established a nomogram prediction model. Methods: Totally 734 elderly patients with hip fractures who underwent surgical treatment (January 2016-December 2020) were enrolled. Following analyses on demographic variables, clinical characteristics, and laboratory examination, independent risk factors of contralateral hip fractures in the elderly were identified through the least absolute shrinkage and selection operator (LASSO) regression, and univariate and multivariate logistic regression. Patients were randomly allocated into training (n = 513) and validation sets (n = 221). A training set-based nomogram prediction model was established and assessed for predictability, discriminatory ability, and clinical applicability using the receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) in both sets. Results: Contralateral hip refractures occurred in 7.08% (52/734) patients within 2 years after surgery. Age, hemoglobin (Hb), heart disease, neurovascular disease, Parkinson's disease (PD), Alzheimer's disease (AD), chronic obstructive pulmonary disease (COPD), and chronic kidney disease (CKD) were independent risk factors. The nomogram prediction model had a favorable discriminatory ability, as indicated by the areas under the ROC curves (AUC): 0.906 (95% CI, 0.845-0.967) in the training set and 0.956 (95% CI, 0.927-0.985) in the validation set. The calibration curves demonstrated a good consistency between the actual subsequent contralateral hip fracture incidence and the predicted probability. The DCA of the nomogram demonstrated the model's excellent clinical efficacy. Conclusion: The nomogram model enabled accurate individualized prediction for the occurrence of subsequent contralateral hip fracture in the elderly within 2 years after surgical treatment, which might help clinicians with precise references for appropriate perioperative management and rehabilitation education following initial hip surgery for their patients.

13.
Biochem Pharmacol ; 218: 115854, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37863324

RESUMEN

Ribonucleotide reductase (RR) is a rate-limiting enzyme that facilitates DNA replication and repair by reducing nucleotide diphosphates (NDPs) to deoxyribonucleotide diphosphates (dNDPs) and is thereby crucial for cell proliferation and cancer development. The E2F family of transcription factors includes key regulators of gene expression involved in cell cycle control. In this study, E2F8 expression was significantly increased in most cancer tissues of lung adenocarcinoma (LUAD) patients and was correlated with the expression of RRM2 through database and clinical samples analysis. The protein expression of E2F8 and RRM2 were positively correlated with tumor-node-metastasis (TNM) pathological stage, and high expression of E2F8 and RRM2 predicted a low 5-year overall survival rate in LUAD patients. Overexpression and knockdown experiments showed that E2F8 was essential for LUAD cell proliferation, DNA synthesis, and cell cycle progression, which were RRM2-dependent. Reporter gene, ChIP-qPCR, and DNA pulldown-Western blot assays indicated that E2F8 activated the transcription of the RRM2 gene by directly binding with the RRM2 promoter in LUAD cells. Previous studies indicated that inhibition of WEE1 kinase can suppress the phosphorylation of CDK1/2 and promote the degradation of RRM2. We further showed here that the combination of E2F8 knockdown with MK-1775, an inhibitor of WEE1 being evaluated in clinical trials, synergistically suppressed proliferation and promoted apoptosis of LUAD cells in vitro and in vivo. Thus, this study reveals a novel role of E2F8 as a proto-oncogenic transcription activator by activating RRM2 expression in LUAD, and targeting both the transcription and degradation mechanisms of RRM2 could produce a synergistic inhibitory effect for LUAD treatment in addition to conventional inhibition of RR enzyme activity.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Proliferación Celular , ADN , Replicación del ADN , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Proteínas Tirosina Quinasas/genética , Proteínas Tirosina Quinasas/metabolismo , Proteínas Represoras/metabolismo
14.
Front Med (Lausanne) ; 10: 1219830, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37465641

RESUMEN

Introduction: Osteoarthritis (OA) refers to a commonly seen degenerative joint disorder and a major global public health burden. According to the existing literature, osteoarthritis is related to epigenetic changes, which are important for diagnosing and treating the disease early. Through early targeted treatment, costly treatments and poor prognosis caused by advanced osteoarthritis can be avoided. Methods: This study combined gene differential expression analysis and weighted gene co-expression network analysis (WGCNA) of the transcriptome with epigenome microarray data to discover the hub gene of OA. We obtained 2 microarray datasets (GSE114007, GSE73626) in Gene Expression Omnibus (GEO). The R software was utilized for identifying differentially expressed genes (DEGs) and differentially methylated genes (DMGs). By using WGCNA to analyze the relationships between modules and phenotypes, it was discovered that the blue module (MEBlue) has the strongest phenotypic connection with OA (cor = 0.92, p = 4e-16). The hub genes for OA, also known as the hub methylated differentially expressed genes, were identified by matching the MEblue module to differentially methylated differentially expressed genes. Furthermore, this study used Gene set variation analysis (GSVA) to identify specific signal pathways associated with hub genes. qRT-PCR and western blotting assays were used to confirm the expression levels of the hub genes in OA patients and healthy controls. Results: Three hub genes were discovered: HTRA1, P2RY6, and RCAN1. GSVA analysis showed that high HTRA1 expression was mainly enriched in epithelial-mesenchymal transition and apical junction; high expression of P2RY6 was mainly enriched in the peroxisome, coagulation, and epithelial-mesenchymal transition; and high expression of RCAN1 was mainly enriched in epithelial-mesenchymal-transition, TGF-ß-signaling, and glycolysis. The results of the RT-qPCR and WB assay were consistent with the findings. Discussion: The three genes tested may cause articular cartilage degeneration by inducing chondrocyte hypertrophy, regulating extracellular matrix accumulation, and improving macrophage pro-inflammatory response, resulting in the onset and progression of osteoarthritis. They can provide new ideas for targeted treatment of osteoarthritis.

15.
Nat Biomed Eng ; 7(10): 1321-1334, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37127710

RESUMEN

Serial assessment of the biomechanical properties of tissues can be used to aid the early detection and management of pathophysiological conditions, to track the evolution of lesions and to evaluate the progress of rehabilitation. However, current methods are invasive, can be used only for short-term measurements, or have insufficient penetration depth or spatial resolution. Here we describe a stretchable ultrasonic array for performing serial non-invasive elastographic measurements of tissues up to 4 cm beneath the skin at a spatial resolution of 0.5 mm. The array conforms to human skin and acoustically couples with it, allowing for accurate elastographic imaging, which we validated via magnetic resonance elastography. We used the device to map three-dimensional distributions of the Young's modulus of tissues ex vivo, to detect microstructural damage in the muscles of volunteers before the onset of soreness and to monitor the dynamic recovery process of muscle injuries during physiotherapies. The technology may facilitate the diagnosis and treatment of diseases affecting tissue biomechanics.

16.
Cell Death Dis ; 13(3): 228, 2022 03 11.
Artículo en Inglés | MEDLINE | ID: mdl-35277481

RESUMEN

Transcription factors, cofactors, chromatin regulators, and transcription apparatuses interact with transcriptional regulatory elements, including promoters, enhancers, and super-enhancers (SEs), to coordinately regulate the transcription of target genes and thereby control cell behaviors. Among these transcriptional regulatory components and related elements, SEs often play a central role in determining cell identity and tumor initiation and progression. Therefore, oncogenic SEs, which are generated within cancer cells in oncogenes and other genes important in tumor pathogenesis, have emerged as attractive targets for novel cancer therapeutic strategies in recent years. Herein, we review the identification, formation and activation modes, and regulatory mechanisms for downstream genes and pathways of oncogenic SEs. We also review the therapeutic strategies and compounds targeting oncogenic SEs in colorectal cancer and other malignancies.


Asunto(s)
Neoplasias Colorrectales , Secuencias Reguladoras de Ácidos Nucleicos , Carcinogénesis/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/terapia , Elementos de Facilitación Genéticos/genética , Humanos , Oncogenes , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
17.
Cancers (Basel) ; 14(19)2022 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-36230632

RESUMEN

Acute myeloid leukaemia (AML) is one of the most common types of haematopoietic malignancy. Ribonucleotide reductase (RNR) is a key enzyme required for DNA synthesis and cell proliferation, and its small subunit RRM2 plays a key role for the enzymatic activity. We predicted monobenzone (MB) as a potential RRM2 target compound based on the crystal structure of RRM2. In vitro, MB inhibited recombinant RNR activity (IC50 = 0.25 µM). Microscale thermophoresis indicated that MB inhibited RNR activity by binding to RRM2. MB inhibited cell proliferation (MTT IC50 = 6-18 µM) and caused dose-dependent DNA synthesis inhibition, cell cycle arrest, and apoptosis in AML cells. The cell cycle arrest was reversed by the addition of deoxyribonucleoside triphosphates precursors, suggesting that RNR was the intracellular target of the compound. Moreover, MB overcame drug resistance to the common AML drugs cytarabine and doxorubicin, and treatment with the combination of MB and the Bcl-2 inhibitor ABT-737 exerted a synergistic inhibitory effect. Finally, the nude mice xenografts study indicated that MB administration produced a significant inhibitory effect on AML growth with relatively weak toxicity. Thus, we propose that MB has the potential as a novel anti-AML therapeutic agent in the future.

18.
Front Bioeng Biotechnol ; 10: 1047902, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36394019

RESUMEN

Purpose: To compare biomechanical and clinical properties of the novel internal fixation Interlocking Hip Screw (IHS) and conventional inverted triangle cannulated screws (ITCS) for treatment of Pauwels Ⅲ femoral neck fractures. Methods: Twenty synthetic femurs were osteotomized to simulate 70° Pauwels Ⅲ femoral neck fractures and randomly divided into two groups: Group IHS and Group ITCS. Specimens were loaded in quasi-static ramped and cyclical compression testing in 25° adduction to analyze for axial stiffness, failure load, and interfragmentary displacement. 21 matched patients with Pauwels Ⅲ femoral neck fracture who received closed reduction and internal fixation from January 2020 to January 2021 in both Group IHS and Group ITCS. Demographic data, time to surgery, operating duration, intraoperative blood loss, number of fluoroscopies, length of hospital stay, fracture healing time, Harris Hip Score (HHS), the score of Visual Analogue Scale (VAS) and complications such as nonunion, avascular necrosis, and femoral neck shortening were compared. Results: All specimens in the two groups survived in the axial and cyclical compression test. The axial stiffness was significantly higher for Group IHS (277.80 ± 26.58 N/mm) versus Group ITCS (205.33 ± 10.46 N/mm), p < 0.05. The maximum failure loading in Group IHS performed significantly higher than in Group ITCS (1,400.48 ± 71.60 N versus 996.76 ± 49.73 N, p < 0.05). The interfragmentary displacement of the cyclic loading test for Groups IHS and Group ITCS was 1.15 ± 0.11 mm and 1.89 ± 0.14 mm, respectively, p < 0.05. No significant difference was found in terms of demographic data, time to surgery, intraoperative blood loss, length of hospital stay and the occurrence of nonunion and avascular necrosis between groups. Shorter operating duration and fewer intraoperative fluoroscopic views were noticed using IHS compare to ITCS, p < 0.05. The HHS was 72.14 ± 5.76 and 86.62 ± 5.01 in Group IHS, and was 67.29 ± 5.27 and 81.76 ± 5.13 in Group ITCS at 3-month and 6-month follow-up, respectively, p < 0.05. The magnitude of femoral neck shortening was significantly lower in Group IHS compared to Group ITCS (4.80 ± 1.03 mm versus 5.56 ± 1.21 mm, p < 0.05). Conclusion: Our study demonstrated that IHS provided better biomechanical and clinical performance due to its unique biological and biomechanical mechanisms, compared with ITCS. Thus, IHS is a feasible alternative to ITCS for the fixation of Pauwels Ⅲ femoral neck fractures.

19.
Nat Commun ; 13(1): 7757, 2022 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-36522334

RESUMEN

Electronic patches, based on various mechanisms, allow continuous and noninvasive monitoring of biomolecules on the skin surface. However, to date, such devices are unable to sense biomolecules in deep tissues, which have a stronger and faster correlation with the human physiological status than those on the skin surface. Here, we demonstrate a photoacoustic patch for three-dimensional (3D) mapping of hemoglobin in deep tissues. This photoacoustic patch integrates an array of ultrasonic transducers and vertical-cavity surface-emitting laser (VCSEL) diodes on a common soft substrate. The high-power VCSEL diodes can generate laser pulses that penetrate >2 cm into biological tissues and activate hemoglobin molecules to generate acoustic waves, which can be collected by the transducers for 3D imaging of the hemoglobin with a high spatial resolution. Additionally, the photoacoustic signal amplitude and temperature have a linear relationship, which allows 3D mapping of core temperatures with high accuracy and fast response. With access to biomolecules in deep tissues, this technology adds unprecedented capabilities to wearable electronics and thus holds significant implications for various applications in both basic research and clinical practice.


Asunto(s)
Imagenología Tridimensional , Transductores , Humanos , Imagenología Tridimensional/métodos , Temperatura , Rayos Láser , Hemoglobinas
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