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1.
Comput Methods Programs Biomed ; 250: 108192, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38701699

RESUMEN

BACKGROUND AND OBJECTIVE: The morbidity of lung adenocarcinoma (LUAD) has been increasing year by year and the prognosis is poor. This has prompted researchers to study the survival of LUAD patients to ensure that patients can be cured in time or survive after appropriate treatment. There is still no fully valid model that can be applied to clinical practice. METHODS: We introduced struc2vec-based multi-omics data integration (SBMOI), which could integrate gene expression, somatic mutations and clinical data to construct mutation gene vectors representing LUAD patient features. Based on the patient features, the random survival forest (RSF) model was used to predict the long- and short-term survival of LUAD patients. To further demonstrate the superiority of SBMOI, we simultaneously replaced scale-free gene co-expression network (FCN) with a protein-protein interaction (PPI) network and a significant co-expression network (SCN) to compare accuracy in predicting LUAD patient survival under the same conditions. RESULTS: Our results suggested that compared with SCN and PPI network, the FCN based SBMOI combined with RSF model had better performance in long- and short-term survival prediction tasks for LUAD patients. The AUC of 1-year, 5-year, and 10-year survival in the validation dataset were 0.791, 0.825, and 0.917, respectively. CONCLUSIONS: This study provided a powerful network-based method to multi-omics data integration. SBMOI combined with RSF successfully predicted long- and short-term survival of LUAD patients, especially with high accuracy on long-term survival. Besides, SBMOI algorithm has the potential to combine with other machine learning models to complete clustering or stratificational tasks, and being applied to other diseases.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/mortalidad , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Pronóstico , Mutación , Mapas de Interacción de Proteínas/genética , Análisis de Supervivencia , Algoritmos , Masculino , Femenino , Biología Computacional/métodos , Redes Reguladoras de Genes , Regulación Neoplásica de la Expresión Génica , Perfilación de la Expresión Génica , Multiómica
2.
Int J Biol Macromol ; 267(Pt 1): 131417, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38582457

RESUMEN

Bone morphogenetic protein 15 (BMP15) plays a crucial role in the porcine follicular development. However, its exact functions in the in vitro maturation (IVM) of porcine oocytes remain largely unknown. Here, through cytoplasmic injection of a preassembled crRNA-tracrRNA-Cas9 ribonucleoprotein complex, we achieved BMP15 disruption in approximately 54 % of the cultured porcine oocytes. Editing BMP15 impaired the IVM of porcine oocytes, as indicated by the significantly increased abnormal spindle assembly and reduced first polar body (PB1) extrusion. The editing also impaired cytoplasmic maturation of porcine oocytes, as reflected by reduced abundant of Golgi apparatus and impaired functions of mitochondria. The impaired IVM of porcine oocytes by editing BMP15 possibly was associated with the attenuated SMAD1/5 and EGFR-ERK1/2 signaling in the cumulus granulosa cells (CGCs) and the inhibited MOS/ERK1/2 signaling in oocytes. The attenuated MOS/ERK1/2 signaling may contribute to the inactivation of maturation promoting factor (MPF) and the increased abnormal spindle assembly, leading to reduced PB1 extrusion. It also may contribute to reduced Golgi apparatus formation, and impaired functions of mitochondria. These findings expand our understanding of the regulatory role of BMP15 in the IVM of porcine oocytes and provide a basis for manipulation of porcine reproductive performance.


Asunto(s)
Proteína Morfogenética Ósea 15 , Oocitos , Huso Acromático , Animales , Oocitos/metabolismo , Proteína Morfogenética Ósea 15/genética , Proteína Morfogenética Ósea 15/metabolismo , Porcinos , Femenino , Huso Acromático/metabolismo , Sistema de Señalización de MAP Quinasas , Mitocondrias/metabolismo , Técnicas de Maduración In Vitro de los Oocitos , Aparato de Golgi/metabolismo , Orgánulos/metabolismo , Orgánulos/genética , Transducción de Señal
3.
Adv Sci (Weinh) ; : e2400207, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38655847

RESUMEN

Wearable sensors hold immense potential for real-time and non-destructive sensing of volatile organic compounds (VOCs), requiring both efficient sensing performance and robust mechanical properties. However, conventional colorimetric sensor arrays, acting as artificial olfactory systems for highly selective VOC profiling, often fail to meet these requirements simultaneously. Here, a high-performance wearable sensor array for VOC visual detection is proposed by extrusion printing of hybrid inks containing surface-functionalized sensing materials. Surface-modified hydrophobic polydimethylsiloxane (PDMS) improves the humidity resistance and VOC sensitivity of PDMS-coated dye/metal-organic frameworks (MOFs) composites. It also enhances their dispersion within liquid PDMS matrix, thereby promoting the hybrid liquid as high-quality extrusion-printing inks. The inks enable direct and precise printing on diverse substrates, forming a uniform and high particle-loading (70 wt%) film. The printed film on a flexible PDMS substrate demonstrates satisfactory flexibility and stretchability while retaining excellent sensing performance from dye/MOFs@PDMS particles. Further, the printed sensor array exhibits enhanced sensitivity to sub-ppm VOC levels, remarkable resistance to high relative humidity (RH) of 90%, and the differentiation ability for eight distinct VOCs. Finally, the wearable sensor proves practical by in situ monitoring of wheat scab-related VOC biomarkers. This study presents a versatile strategy for designing effective wearable gas sensors with widespread applications.

4.
ACS Appl Mater Interfaces ; 16(15): 19359-19368, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38568140

RESUMEN

Wearable sensors utilize changes in color as a response to physiological stimuli, making them easily recognizable by the naked eye. These colorimetric wearable sensors offer benefits such as easy readability, rapid responsiveness, cost-effectiveness, and straightforward manufacturing techniques. However, their applications in detecting volatile organic compounds (VOCs) in situ have been limited due to the low concentration of complex VOCs and complicated external interferences. Aiming to address these challenges, we introduced readable and wearable colorimetric sensing arrays with a microchannel structure and highly gas-sensitive materials for in situ detection of complex VOCs. The highly gas-sensitive materials were designed by loading gas-sensitive dyes into the porous metal-organic frameworks and further depositing the composites on the electrospun nanofiber membrane. The colorimetric sensor arrays were fabricated using various gas-sensitive composites, including eight dye/MOF composites that respond to various VOCs and two Pd2+/dye/MOF composites that respond to ethylene. This enables the specific recognition of multiple characteristic VOCs. A microfluidic channel made of polydimethylsiloxane (PDMS) was integrated with different colorimetric elements to create a wearable sensor array. It was attached to the surface of fruits to collect and monitor VOCs using the DenseNet classification method. As a proof of concept, we demonstrated the feasibility of the wearable sensing system in monitoring the ripening process of fruits by continuously measuring the VOC emissions from the skin of the fruit.


Asunto(s)
Compuestos Orgánicos Volátiles , Dispositivos Electrónicos Vestibles , Colorimetría/métodos , Comprensión , Piel , Colorantes
5.
J Inflamm Res ; 17: 1995-2008, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38566983

RESUMEN

Background: Long non-coding RNAs (lncRNAs) associated with immunogenic cell death (ICD) play a pivotal role in tumorigenesis and offer prognostic insights for papillary thyroid carcinoma (PTC) patients. This study delves into the impact of ICD-related lncRNAs on the prognosis of PTC. Methods: PTC samples were accessed from The Cancer Genome Atlas-Thyroid carcinoma database (TCGA-THCA) and consensus cluster analysis to elucidate the influence of ICD-related lncRNA expression. To gauge the prognostic significance of these lncRNAs, we developed a prognostic model. Additionally, we conducted GO and KEGG enrichment analyses, assessed immune cell infiltration (ICI) using CIBERSORT and ssGSEA, examined immune checkpoint expression, tumor mutation burden (TMB), tumor microenvironment (TME), T-cell dysfunction and exclusion (TIDE), TCIA, and drug sensitivity across various groups. A comprehensive suite of in vitro experiments, encompassing EdU labeling, wound scratch assays, Transwell assays, and flow cytometry, were conducted to elucidate the regulatory role of LINC00924 in two PTC cell lines, BCPAP and TPC1, transfected with LINC00924 overexpression plasmids. Results: Two distinct clusters demonstrated varying TME, BRAF, NRAS, and ICI characteristics, suggesting potential immune mechanisms in PTC. Our prognostic model identified seven lncRNAs: SRRM2-AS1, AC008556.1, BHLHE40-AS1, EGOT, AL39066.1, LINC00924, and PICART1. The expression of ICD-related lncRNAs correlated with progression-free interval (PFI) in PTC patients. Overexpression of LINC00924 significantly reduced cell proliferation, migration, and invasion, while augmenting apoptosis in PTC cells. Conclusion: Our findings highlight the potential of ICD-related lncRNAs as prognostic biomarkers for PFI in PTC. In vitro experiments suggest a protective role of LINC00924 in PTC progression.

6.
Mol Ther ; 32(5): 1219-1237, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38449313

RESUMEN

Bone cancer is common and severe. Both primary (e.g., osteosarcoma, Ewing sarcoma) and secondary (e.g., metastatic) bone cancers lead to significant health problems and death. Currently, treatments such as chemotherapy, hormone therapy, and radiation therapy are used to treat bone cancer, but they often only shrink or slow tumor growth and do not eliminate cancer completely. The bone microenvironment contributes unique signals that influence cancer growth, immunogenicity, and metastasis. Traditional cancer therapies have limited effectiveness due to off-target effects and poor distribution on bones. As a result, therapies with improved specificity and efficacy for treating bone tumors are highly needed. One of the most promising strategies involves the targeted delivery of pharmaceutical agents to the site of bone cancer by introduction of bone-targeting moieties, such as bisphosphonates or oligopeptides. These moieties have high affinities to the bone hydroxyapatite matrix, a structure found exclusively in skeletal tissue, and can enhance the targeting ability and efficacy of anticancer drugs when combating bone tumors. This review focuses on the engineering of small molecules and proteins with bone-targeting moieties for the treatment of bone tumors.


Asunto(s)
Antineoplásicos , Neoplasias Óseas , Humanos , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/terapia , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Animales , Difosfonatos/uso terapéutico , Difosfonatos/farmacología , Difosfonatos/química , Sistemas de Liberación de Medicamentos/métodos , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/patología , Sarcoma de Ewing/tratamiento farmacológico , Sarcoma de Ewing/terapia , Terapia Molecular Dirigida/métodos , Microambiente Tumoral/efectos de los fármacos
7.
Adv Mater ; : e2312508, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38465829

RESUMEN

Sodium foil, promising for high-energy-density batteries, faces reversibility challenges due to its inherent reactivity and unstable solid electrolyte interphase (SEI) layer. In this study, a stable sodium metal battery (SMB) is achieved by tuning the electrolyte solvation structure through the addition of co-solvent 2-methyl tetrahydrofuran (MTHF) to diglyme (Dig). The introduction of cyclic ether-based MTHF results in increased anion incorporation in the solvation structure, even at lower salt concentrations. Specifically, the anion stabilization capabilities of the environmentally sustainable MTHF co-solvent lead to a contact-ion pair-based solvation structure. Time-of-flight mass spectroscopy analysis reveals that a shift toward an anion-dominated solvation structure promotes the formation of a thin and uniform SEI layer. Consequently, employing a NaPF6-based electrolyte with a Dig:MTHF ratio of 50% (v/v) binary solvent yields an average Coulombic efficiency of 99.72% for 300 cycles in Cu||Na cell cycling. Remarkably, at a C/2 cycling rate, Na||Na symmetric cell cycling demonstrates ultra-long-term stability exceeding 7000 h, and full cells with Na0.44MnO2 as a cathode retain 80% of their capacity after 500 cycles. This study systematically examines solvation structure, SEI layer composition, and electrochemical cycling, emphasizing the significance of MTHF-based binary solvent mixtures for high-performance SMBs.

8.
Foods ; 13(5)2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38472906

RESUMEN

Artificial scent screening systems, inspired by the mammalian olfactory system, hold promise for fruit ripeness detection, but their commercialization is limited by low sensitivity or pattern recognition inaccuracy. This study presents a portable fruit ripeness prediction system based on colorimetric sensing combinatorics and deep convolutional neural networks (DCNN) to accurately identify fruit ripeness. Using the gas chromatography-mass spectrometry (GC-MS) method, the study discerned the distinctive gases emitted by mango, peach, and banana across various ripening stages. The colorimetric sensing combinatorics utilized 25 dyes sensitive to fruit volatile gases, generating a distinct scent fingerprint through cross-reactivity to diverse concentrations and varieties of gases. The unique scent fingerprints can be identified using DCNN. After capturing colorimetric sensor image data, the densely connected convolutional network (DenseNet) was employed, achieving an impressive accuracy rate of 97.39% on the validation set and 82.20% on the test set in assessing fruit ripeness. This fruit ripeness prediction system, coupled with a DCNN, successfully addresses the issues of complex pattern recognition and low identification accuracy. Overall, this innovative tool exhibits high accuracy, non-destructiveness, practical applicability, convenience, and low cost, making it worth considering and developing for fruit ripeness detection.

9.
Adv Mater ; : e2307123, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38533973

RESUMEN

Ultrasound imaging and ultrasound-mediated gene and drug delivery are rapidly advancing diagnostic and therapeutic methods; however, their use is often limited by the need for microbubbles, which cannot transverse many biological barriers due to their large size. Here, the authors introduce 50-nm gas-filled protein nanostructures derived from genetically engineered gas vesicles(GVs) that are referred to as 50 nmGVs. These diamond-shaped nanostructures have hydrodynamic diameters smaller than commercially available 50-nm gold nanoparticles and are, to the authors' knowledge, the smallest stable, free-floating bubbles made to date. 50 nmGVs can be produced in bacteria, purified through centrifugation, and remain stable for months. Interstitially injected 50 nmGVs can extravasate into lymphatic tissues and gain access to critical immune cell populations, and electron microscopy images of lymph node tissues reveal their subcellular location in antigen-presenting cells adjacent to lymphocytes. The authors anticipate that 50 nmGVs can substantially broaden the range of cells accessible to current ultrasound technologies and may generate applications beyond biomedicine as ultrasmall stable gas-filled nanomaterials.

10.
Biosens Bioelectron ; 251: 116114, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38354495

RESUMEN

Plant nanobionic sensors enable real-time monitoring of signaling molecules in plants by interfacing them with specifically designed nanoprobes, which have been acknowledged as species-independent analytical tools. In this study, we developed a plant nanobionic sensor for in vivo detection of extracellular adenosine triphosphate (eATP) in living plants by designing a novel second near-infrared (NIR-II) fluorescent metal-organic framework (MOF) nanoprobe. The NIR-II fluorescent nanoprobe (IR-1061 micelle@ZIF-90) with a sandwich structure was synthesized by successive encapsulation of the hydrophobic NIR-II dye IR-1061 with the amphipathic polymer DSPE-mPEG 2000 and MOF ZIF-90. Interestingly, coating ZIF-90 around IR-1061 micelles increased the NIR-II fluorescence 16.6-fold. Utilizing the ultrahigh NIR-II fluorescent emission of the designed nanoprobes and specific recognition of ZIF-90 to ATP, the nanoprobes were applied to spatial and temporal monitoring eATP in model and non-model plants under environmental stress.


Asunto(s)
Técnicas Biosensibles , Boratos , Estructuras Metalorgánicas , Nanopartículas , Piranos , Estructuras Metalorgánicas/química , Adenosina Trifosfato , Colorantes Fluorescentes/química
11.
Funct Integr Genomics ; 24(1): 27, 2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38332346

RESUMEN

ZMIZ1 acts as an oncogene in hepatocellular carcinoma (HCC). circZMIZ1 (hsa_circ_0018964) derives from ZMIZ1; its underlying mechanism in HCC has not been reported. Peripheral blood and peripheral blood mononuclear cells (PBMCs) were obtained from HCC patients and healthy volunteers. CD8+ T cells were sorted from PBMCs of HCC patients. Applying flow cytometry, cell apoptosis and the proportion of KCNJ2/CD8+ T cells were examined. The cytotoxicity of CD8+ T cells against HCC cells was evaluated. The interaction among circZMIZ1, miR-15a-5p, and KCNJ2 was investigated by dual luciferase assay, RNA immunoprecipitation, and RNA pull-down assay. An orthotopic mouse model of HCC was constructed by intrahepatic injection of H22 cells. Upregulation of circZMIZ1 and KCNJ2 and downregulation of miR-15a-5p were observed in peripheral blood and PBMCs of HCC patients. The proportion of KCNJ2/CD8+ T cells was also increased in HCC patients. circZMIZ1 knockdown restrained apoptosis of CD8+ T cells and elevated cytotoxicity of CD8+ T cells. Mechanically speaking, circZMIZ1 elevated KCNJ2 expression by sponging miR-15a-5p. miR-15a-5p inhibitor reversed circZMIZ1 silencing-mediated inhibition of apoptosis and promotion of cytotoxicity in CD8+ T cells. In vivo, orthotopic mice of HCC exhibited increased expression of circZMIZ1 and KCNJ2, elevated proportion of KCNJ2/CD8+ T cells, and decreased expression of miR-15a-5p. This work demonstrated that circZMIZ1 inhibited the anti-tumor activity of CD8+ T cells in HCC by regulating the miR-15a-5p/KCNJ2 axis. This provides a theoretical basis for the development of effective circZMIZ1 in tumor immunotherapy.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , Animales , Humanos , Ratones , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Linfocitos T CD8-positivos/patología , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Leucocitos Mononucleares/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , MicroARNs/genética
12.
Proc Natl Acad Sci U S A ; 121(5): e2312929121, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38252825

RESUMEN

Immunotherapy is a promising approach for treating metastatic breast cancer (MBC), offering new possibilities for therapy. While checkpoint inhibitors have shown great progress in the treatment of metastatic breast cancer, their effectiveness in patients with bone metastases has been disappointing. This lack of efficacy seems to be specific to the bone environment, which exhibits immunosuppressive features. In this study, we elucidate the multiple roles of the sialic acid-binding Ig-like lectin (Siglec)-15/sialic acid glyco-immune checkpoint axis in the bone metastatic niche and explore potential therapeutic strategies targeting this glyco-immune checkpoint. Our research reveals that elevated levels of Siglec-15 in the bone metastatic niche can promote tumor-induced osteoclastogenesis as well as suppress antigen-specific T cell responses. Next, we demonstrate that antibody blockade of the Siglec-15/sialic acid glyco-immune checkpoint axis can act as a potential treatment for breast cancer bone metastasis. By targeting this pathway, we not only aim to treat bone metastasis but also inhibit the spread of metastatic cancer cells from bone lesions to other organs.


Asunto(s)
Neoplasias Óseas , Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Ácido N-Acetilneuramínico , Neoplasias Óseas/tratamiento farmacológico , Inmunoterapia , Anticuerpos Bloqueadores
13.
Cell Chem Biol ; 31(3): 428-445, 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-37802076

RESUMEN

Recent years have seen a remarkable growth in the field of protein-based medical treatments. Nevertheless, concerns have arisen regarding the cytotoxicity limitations, low affinity, potential immunogenicity, low stability, and challenges to modify these proteins. To overcome these obstacles, proximity-induced chemistry has emerged as a next-generation strategy for advancing protein therapeutics. This method allows site-specific modification of proteins with therapeutic agents, improving their effectiveness without extensive engineering. In addition, this innovative approach enables spatial control of the reaction based on proximity, facilitating the formation of irreversible covalent bonds between therapeutic proteins and their targets. This capability becomes particularly valuable in addressing challenges such as the low affinity frequently encountered between therapeutic proteins and their targets, as well as the limited availability of small molecules for specific protein targets. As a result, proximity-induced chemistry is reshaping the field of protein drug preparation and propelling the revolution in novel protein therapeutics.


Asunto(s)
Proteínas
14.
JMIR Public Health Surveill ; 9: e39472, 2023 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-38079213

RESUMEN

BACKGROUND: The World Health Organization has proposed a worldwide target of eliminating hepatitis C virus (HCV) by 2030. A better understanding of HCV, testing behaviors, and associated factors in the general population is essential. OBJECTIVE: This study aimed to assess HCV knowledge, self-reported HCV testing behavior, and willingness to undergo HCV screening in the general Chinese population. METHODS: A cross-sectional online survey of the general Chinese population aged ≥15 years was conducted from November 2021 to May 2023. Participant characteristics were assessed based on their knowledge level and uptake of HCV testing. Participants ever having heard of HCV were recognized as being aware of HCV and asked additional HCV knowledge questions using a brief, validated 9-item scale. Participants with 0-3 points and who were unaware of HCV were categorized as having poor knowledge, and those with 4-6 points and 7 points were categorized as having fair and good knowledge, respectively. Participant uptake of HCV testing, testing results, reasons for undergoing or not undergoing HCV testing, and willingness to undergo HCV screening were collected through self-reports. Ordinal and binary logistic regression analyses were used to assess factors associated with the HCV knowledge level and the uptake of HCV testing, respectively. RESULTS: A total of 1491 valid participants' questionnaires were included. Of these, 714 (47.6%) participants were aware of HCV. The proportion of participants with poor, fair, and good HCV knowledge was 63.4% (945/1491), 9.3% (139/1491), and 27.3% (407/1491), respectively. A total of 465 (31.2%) participants reported ever undergoing HCV testing, and 4 (0.9%) were anti-HCV antibody positive. Most participants were tested for HCV following blood donation (353/465, 75.9%). The most common reasons for not undergoing HCV screening were a lack of HCV awareness (665/1026, 64.8%), followed by a low self-perceived risk of infection (176/1026, 17.2%). Of 1026 participants who had never undergone HCV testing, 937 (91.3%) were willing to undergo HCV screening if universal screening was provided at no cost. The HCV knowledge level was positively associated with the HCV testing rate. Participants who were less educated, lived in rural areas, resided in West China, and were currently alcohol drinkers had lower HCV knowledge and reduced odds of having undergone HCV testing. In contrast, participants with a blood donation history and a family history of hepatitis B virus or HCV infection had higher HCV knowledge and increased odds of prior testing. Participants aged ≥60 years had lower knowledge, and women had reduced odds of having undergone previous HCV testing. CONCLUSIONS: The general population of China has low HCV knowledge and testing rate. There is an urgent need for enhanced HCV awareness and scaled-up HCV screening and treatment. Individuals who are less well educated, reside in less-developed areas, currently drink alcohol, and are female should be prioritized for health education and interventions.


Asunto(s)
Infecciones por VIH , Hepatitis C , Humanos , Femenino , Masculino , Hepacivirus , Estudios Transversales , Autoinforme , Infecciones por VIH/epidemiología , Hepatitis C/diagnóstico , Hepatitis C/epidemiología , Hepatitis C/complicaciones , China/epidemiología
15.
Front Neurosci ; 17: 1304150, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38116072

RESUMEN

Background: In order to improve the safety of lumbar puncture (LP), we designed a new type of LP needle, that is, an integrated and controlled LP needle, which can actively and accurately control the flow rate and retention of cerebrospinal fluid (CSF) during puncture, so as to achieve a controlled LP procedure. Objective: To evaluate whether a controlled LP procedure can improve the comfort of LP and reduce the risk of complications associated with LP. Methods: Patients requiring LP (n = 63) were pierced with an integrated and controlled LP needle or a conventional LP needle. The differences in vital signs, symptom score, comfort, operation time, CSF loss, CSF pressure fluctuation and back pain before and after puncture were analyzed. Results: An integrated and controlled LP needle (n = 35) significantly improved patients' headache symptoms before and after puncture. In addition, a controlled LP procedure significantly reduced the amount of unnecessary CSF loss (p < 0.001), shortened the time of puncture (p < 0.001), improved patient comfort (p = 0.001) and reduced the incidence of back pain (p < 0.001). For patients with high intracranial pressure (HICP), the fluctuations in pressure of the CSF were also reduced while obtaining similar amounts of CSF (p = 0.009). Conclusion: A controlled LP procedure avoids unnecessary CSF loss, prevents rapid fluctuations in CSF pressure in patients with HICP, and reduces the risks associated with LP.

16.
Adv Sci (Weinh) ; 10(23): e2207651, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37310418

RESUMEN

Chemiluminescence (CL) imaging, as an excitation-free technique, exhibits a markedly improved signal-to-noise ratio (SNR) owing to the absence of an excitation light source and autofluorescence interference. However, conventional chemiluminescence imaging generally focuses on the visible and first near-infrared (NIR-I) regions, which hinders high-performance biological imaging due to strong tissue scattering and absorption. To address the issue, self-luminescent NIR-II CL nanoprobes with a second near-infrared (NIR-II) luminescence in the presence of hydrogen peroxide are rationally designed. A cascade energy transfer, including chemiluminescence resonance energy transfer (CRET) from the chemiluminescent substrate to NIR-I organic molecules and Förster resonance energy transfer (FRET) from NIR-I organic molecules to NIR-II organic molecules, occurs in the nanoprobes, contributing to NIR-II light with great efficiency and good tissue penetration depth. Based on excellent selectivity, high sensitivity to hydrogen peroxide, and long-lasting luminescence performance, the NIR-II CL nanoprobes are applied to detect inflammation in mice, showing a 7.4-fold enhancement in SNR compared with that of fluorescence.


Asunto(s)
Luminiscencia , Nanopartículas , Animales , Ratones , Nanopartículas/química , Peróxido de Hidrógeno , Diagnóstico por Imagen , Fluorescencia
17.
Mol Med Rep ; 28(2)2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37350394

RESUMEN

Acute myeloid leukemia (AML) is a clonal malignant proliferative disease. In recent years, with the use of all­trans retinoic acid to induce cancer cell differentiation in acute promyelocytic leukemia, and its advantages of high efficacy and low toxic side effects, tumor differentiation therapy has become a research hotspot; however, the mechanisms underlying its role remain to be fully established. Nod­like receptor family pyridine domain containing 3 (NLRP3) is the most extensively studied and well­characterized inflammasome, is involved in a variety of inflammation­related diseases, including cancer, and is a very attractive potential target for the study of novel therapeutic agents. Activation of the NLRP3 inflammasome is a double­edged sword in tumor therapy, with evidence of protective anti­tumor and pro­tumor effects in different types of cancer. Whether the NLRP3 inflammasome promotes disease progression or exerts a protective anti­tumor effect in hematological malignancies remains contested. In the present study, the protective anti­tumor effects of NLRP3 on leukemia cells during their differentiation and maturation were investigated. It was found that the upregulation of NLRP3 expression induced using Phorbol 12­Myristate 13­Acetate played a role in promoting the differentiation and maturation of leukemia cells into monocytes/macrophages, and it was directly involved in the apoptosis of leukemia cells and the differentiation and maturation of CD11b+ cells. These results provide novel theoretical evidence for exploring the mechanism of differentiation therapy in leukemia and improves our understanding of the role of NLRP3 in hematologic tumors.


Asunto(s)
Inflamasomas , Leucemia , Humanos , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Apoptosis , Diferenciación Celular
18.
Sci Total Environ ; 876: 163213, 2023 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-37011696

RESUMEN

Drying-induced cracks negatively impacts the performance of soils in the context of global warming. Traditional testing approaches used for the cracking characterization of soils are mainly based on surface observation and qualitative inspections. In this study, a temporal investigation of micron-sized X-ray computed tomography (Micro-CT) tests was performed on the granite residual soil (GRS) during desiccation for the first time. Through three-dimensional (3D) reconstructions and seepage simulations, the dynamic evolution of drying-induced cracks and permeability that evolved (0 to 120 h) was visually characterized and intensively quantified. Experimental results show that the averaged area-porosity ratio varies as an increasing trend, appearing fast at first and slowly thereafter during desiccation.. Observed by 3D reconstruction models, connected cracks rapidly propagated through the samples while isolated cracks occupied small volumes and remained almost unchanged. The pore-diameter distribution of GRS reveals that the propagation of connected cracks is essential in influencing soil cracking. The simulated permeability is generally comparable with measuring ones with an acceptable error margin, demonstrating the accuracy of seepage models. The increasing permeability from both experiments and numerical simulations indicates the desiccation process severely impacts the hydraulic properties of soils. This study provides an adamant evidence that the Micro-CT is an effective and feasible tool for the elucidation of drying-induced crack evolutions and in building numerical models for permeability validation.

19.
Anal Bioanal Chem ; 415(18): 4557-4567, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37069445

RESUMEN

Numerous studies have linked a wide range of diseases including respiratory illnesses to harmful particulate matter (PM) emissions indoors and outdoors, such as incense PM and industrial PM. Because of their ability to penetrate the lower respiratory tract and the circulatory system, fine particles with diameters of 2.5 µm or less (PM2.5) are believed to be more hazardous than larger PMs. Despite the enormous number of studies focusing on the intracellular processes associated with PM2.5 exposure, there have been limited reports studying the biophysical properties of cell membranes, such as nanoscale morphological changes induced by PM2.5. Our study assesses the membrane topographical and structural effects of PM2.5 from incense PM2.5 exposure in real time on A549 lung carcinoma epithelial cells and SH-SY5Y neuroblastoma cells that had been fixed to preclude adaptive cell responses. The size distribution and mechanical properties of the PM2.5 sample were characterized with atomic force microscopy (AFM). Nanoscale morphological monitoring of the cell membranes utilizing scanning ion conductance microscopy (SICM) indicated statistically significant increasing membrane roughness at A549 cells at half an hour of exposure and visible damage at 4 h of exposure. In contrast, no significant increase in roughness was observed on SH-SY5Y cells after half an hour of PM2.5 exposure, although continued exposure to PM2.5 for up to 4 h affected an expansion of lesions already present before exposure commenced. These findings suggest that A549 cell membranes are more susceptible to structural damage by PM2.5 compared to SH-SY5Y cell membranes, corroborating more enhanced susceptibility of airway epithelial cells to exposure to PM2.5 than neuronal cells.


Asunto(s)
Contaminantes Atmosféricos , Neuroblastoma , Humanos , Material Particulado/toxicidad , Contaminantes Atmosféricos/toxicidad , Contaminantes Atmosféricos/análisis , Microscopía , Pulmón/química , Membrana Celular/química
20.
Microb Pathog ; 180: 106111, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37084823

RESUMEN

Cutibacterium acnes (C. acnes) is a symbiotic bacterium that plays an important role in the formation of acn e inflammatory lesions. As a common component of the acne microbiome, C. acnes phages have the potential to make a significant contribution to treating antibiotic-resistant strains of C. acnes. However, little is known about their genetic composition and diversity. In this study, a new lytic phage, Y3Z, infecting C. acne, was isolated and characterized. Electron microscopy analysis revealed this phage is a siphovirus. Phage Y3Z is composed of 29,160 bp with a GC content of 56.32%. The genome contains 40 open reading frames, 17 of which had assigned functions, while no virulence-related genes, antibiotic resistance genes or tRNA were identified. The one-step growth curve showed the burst size was 30 PFU (plaque-forming unit)/cell. And it exhibited tolerance over a broad range of pH and temperature ranges. Phage Y3Z could infect and lyse all C. acnes isolates tested, though the host range of PA6 was restricted to C. acnes. Based on the phylogenetic and comparative genomic analyses, Y3Z may represent a new siphovirus infecting C. acnes. Characterization of Y3Z will enrich our knowledge about the diversity of C. acnes phages and provide a potential arsenal for thetreatment of acne infection.


Asunto(s)
Acné Vulgar , Bacteriófagos , Humanos , Genoma Viral , Filogenia , Propionibacterium acnes/genética , Acné Vulgar/genética , Acné Vulgar/microbiología
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