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1.
Chin Med ; 19(1): 90, 2024 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-38951913

RESUMEN

BACKGROUND: Given the high cost of endoscopy in gastric cancer (GC) screening, there is an urgent need to explore cost-effective methods for the large-scale prediction of precancerous lesions of gastric cancer (PLGC). We aim to construct a hierarchical artificial intelligence-based multimodal non-invasive method for pre-endoscopic risk screening, to provide tailored recommendations for endoscopy. METHODS: From December 2022 to December 2023, a large-scale screening study was conducted in Fujian, China. Based on traditional Chinese medicine theory, we simultaneously collected tongue images and inquiry information from 1034 participants, considering the potential of these data for PLGC screening. Then, we introduced inquiry information for the first time, forming a multimodality artificial intelligence model to integrate tongue images and inquiry information for pre-endoscopic screening. Moreover, we validated this approach in another independent external validation cohort, comprising 143 participants from the China-Japan Friendship Hospital. RESULTS: A multimodality artificial intelligence-assisted pre-endoscopic screening model based on tongue images and inquiry information (AITonguequiry) was constructed, adopting a hierarchical prediction strategy, achieving tailored endoscopic recommendations. Validation analysis revealed that the area under the curve (AUC) values of AITonguequiry were 0.74 for overall PLGC (95% confidence interval (CI) 0.71-0.76, p < 0.05) and 0.82 for high-risk PLGC (95% CI 0.82-0.83, p < 0.05), which were significantly and robustly better than those of the independent use of either tongue images or inquiry information alone. In addition, AITonguequiry has superior performance compared to existing PLGC screening methodologies, with the AUC value enhancing 45% in terms of PLGC screening (0.74 vs. 0.51, p < 0.05) and 52% in terms of high-risk PLGC screening (0.82 vs. 0.54, p < 0.05). In the independent external verification, the AUC values were 0.69 for PLGC and 0.76 for high-risk PLGC. CONCLUSION: Our AITonguequiry artificial intelligence model, for the first time, incorporates inquiry information and tongue images, leading to a higher precision and finer-grained pre-endoscopic screening of PLGC. This enhances patient screening efficiency and alleviates patient burden.

2.
Environ Pollut ; 356: 124346, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38852663

RESUMEN

Triclocarban (TCC) and its metabolite, 3,4-dichloroaniline (DCA), are classified as emerging organic contaminants (EOCs). Significant concerns arise from water and soil contamination with TCC and its metabolites. These concerns are especially pronounced at high concentrations of up to approximately 20 mg/kg dry weight, as observed in wastewater treatment plants (WWTPs). Here, a TCC-degrading co-culture system comprising Rhodococcus rhodochrous BX2 and Pseudomonas sp. LY-1 was utilized to degrade TCC (14.5 mg/L) by 85.9% in 7 days, showing improved degradation efficiency compared with monocultures. A combination of high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), genome sequencing, transcriptomic analysis, and quantitative reverse transcription-PCR (qRT-PCR) was performed. Meanwhile, through the combination of further experiments involving heterologous expression and gene knockout, we proposed three TCC metabolic pathways and identified four key genes (tccG, tccS, phB, phL) involved in the TCC degradation process. Moreover, we revealed the internal labor division patterns and connections in the co-culture system, indicating that TCC hydrolysis products were exchanged between co-cultured strains. Additionally, mutualistic cooperation between BX2 and LY-1 enhances TCC degradation efficiency. Finally, phytotoxicity assays confirmed a significant reduction in the plant toxicity of TCC following synergistic degradation by two strains. The in-depth understanding of the TCC biotransformation mechanisms and microbial interactions provides useful information for elucidating the mechanism of the collaborative biodegradation of various contaminants.

3.
Cell Death Dis ; 15(6): 439, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38906852

RESUMEN

Although adamantinomatous craniopharyngioma (ACP) is a tumour with low histological malignancy, there are very few therapeutic options other than surgery. ACP has high histological complexity, and the unique features of the immunological microenvironment within ACP remain elusive. Further elucidation of the tumour microenvironment is particularly important to expand our knowledge of potential therapeutic targets. Here, we performed integrative analysis of 58,081 nuclei through single-nucleus RNA sequencing and spatial transcriptomics on ACP specimens to characterize the features and intercellular network within the microenvironment. The ACP environment is highly immunosuppressive with low levels of T-cell infiltration/cytotoxicity. Moreover, tumour-associated macrophages (TAMs), which originate from distinct sources, highly infiltrate the microenvironment. Using spatial transcriptomic data, we observed one kind of non-microglial derived TAM that highly expressed GPNMB close to the terminally differentiated epithelial cell characterized by RHCG, and this colocalization was verified by asmFISH. We also found the positive correlation of infiltration between these two cell types in datasets with larger cohort. According to intercellular communication analysis, we report a regulatory network that could facilitate the keratinization of RHCG+ epithelial cells, eventually causing tumour progression. Our findings provide a comprehensive analysis of the ACP immune microenvironment and reveal a potential therapeutic strategy base on interfering with these two types of cells.


Asunto(s)
Craneofaringioma , Neoplasias Hipofisarias , Microambiente Tumoral , Humanos , Craneofaringioma/genética , Craneofaringioma/patología , Craneofaringioma/metabolismo , Craneofaringioma/inmunología , Microambiente Tumoral/inmunología , Neoplasias Hipofisarias/patología , Neoplasias Hipofisarias/genética , Neoplasias Hipofisarias/inmunología , Neoplasias Hipofisarias/metabolismo , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/inmunología , Masculino , Femenino , Queratinas/metabolismo , Transcriptoma/genética , Regulación Neoplásica de la Expresión Génica , Adulto , Persona de Mediana Edad , Multiómica
4.
Anal Chem ; 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38918973

RESUMEN

Both controllable regulation of the conformational structure of a polypeptide and specific recognition of an amino acid are still arduous challenges. Here, a novel dual-mode (electrochemical and colorimetric) biosensor was built for arginine (Arg) recognition based on a conformation switch, utilizing controllable and synergistic self-assembly of a ferrocene-grafted hexadecapeptide (P16Fc) with gold nanoparticles (AuNPs). Benefiting from the flexibility and unique topological structure of P16Fc formed nanospheres, the assembly and disassembly can undergo a conformation transition induced by Arg through controlling the distance and number of Fc detached from the gold surface, producing on-off electrical signals. Also, they can induce aggregation and dispersion of AuNPs in solution, causing a color change. The mechanism of Arg recognition with polypeptide conformation regulation was well explored by combining microstructure characterizations with molecular mechanics calculations. The electrochemical and colorimetric assays for Arg were successfully established in sensitive and selective manner, not only obtaining a very low detection limit, but also effectively eliminating the interference from other amino acids and overcoming the limitation of AuNP aggregation. Notably, the conformational change-based assay with the peptide regulated by the target will make a powerful tool for the amino acid biosensing and health diagnosis.

5.
Clin Neuropharmacol ; 47(3): 87-96, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38743602

RESUMEN

OBJECTIVES: Clinical manifestations of vitamin B12 deficiency are varied and may result in missed or delayed diagnosis. This investigation explores the diverse clinical manifestations and demographic characteristics of vitamin B12 deficiency in neurology outpatients, aiming to enhance timely diagnosis and outcomes. METHODS: The severity of vitamin B12 deficiency was classified as absolute (≤150 pg/mL) or borderline deficiency (150-300 pg/mL). We conducted a retrospective analysis of 165 outpatients with vitamin B12 deficiency at the department of neurology between May 2020 and May 2021. RESULT: Absolute vitamin B12 deficiency was found in 23.0% of the patients. The most common age range was 50-60 years, the most common cause was vegetarianism, and the most common symptom was headache. Epileptiform symptoms were more likely to occur in younger patients (<20 years old) with vitamin B12 deficiency, whereas psychiatric symptoms were more likely to occur in older patients (>70 years old). Vegetarians, salivation, and nonmegaloblastic anemia were more obvious in patients with absolute vitamin B12 deficiency, whereas headaches often showed borderline B12 deficiency. CONCLUSIONS: The clinical characteristics of vitamin B12 deficiency are complex and nonspecific. The diagnosis should be based on multiple factors.


Asunto(s)
Pacientes Ambulatorios , Deficiencia de Vitamina B 12 , Humanos , Deficiencia de Vitamina B 12/complicaciones , Deficiencia de Vitamina B 12/diagnóstico , Deficiencia de Vitamina B 12/epidemiología , Estudios Retrospectivos , Persona de Mediana Edad , Masculino , Femenino , Anciano , Adulto , Adulto Joven , Adolescente , Cefalea/diagnóstico , Anciano de 80 o más Años , Neurología
6.
Artículo en Inglés | MEDLINE | ID: mdl-38781485

RESUMEN

BACKGROUND AND OBJECTIVES: Lateralization or mobilization of the internal carotid artery (ICA) during a midline approach is required to expose lesions behind or lateral to the ICA. However, there have been no published data regarding the surgical outcomes of the endoscopic endonasal internal carotid transposition technique (EEITT). This study aimed to analyze the relevant surgical anatomy around the ICA and propose a grading scheme of EEITT. METHODS: A retrospective review of patients who underwent EEITT at a single institution was performed. Based on structures that limited the ICA and intraoperative findings, an anatomically surgical grading scheme of EEITT was proposed. RESULTS: Forty-two patients (mean age 45.6 years, 57.1% female patients) were included. Of them, 29 cases (69.0%) were Knosp grade 4 pituitary adenoma, 6 cases (14.3%) were chordoma, 6 cases (14.3%) were meningioma, and a single case (2.4%) was meningeal IgG4-related disease. The EEITT was categorized into Grades 1, 2 and 3, which was used in 24 (57.1%), 12 (28.6%), and 6 (14.3%) cases, respectively. The most common symptom was visual disturbance (45.2%). The gross total resection rate in Grade 1 (79.2%) and Grade 2 (83.3%) was much higher than that in Grade 3 (66.6%). The overall rate of visual function improvement, preoperative cranial nerve (CN) palsy improvement, and postoperative hormonal remission was 89.4%, 85.7%, and 88.9%, respectively. The rate for the following morbidities was cerebrospinal fluid leakage, 2.4%; permanent diabetes insipidus, 4.8%; new transient CN palsy, 9.5%; permanent CN palsy, 4.7%; panhypopituitarism, 7.1%; and ICA injury, 2.4%. CONCLUSION: The EEITT is technically feasible and could be graded according to the extent of disconnection of limiting structures. For complex tumor with parasellar extensions, the distinction into Grades 1, 2, and 3 will be of benefit to clinicians in predicting risks, avoiding complications, and generating tailored individualized surgical strategies.

7.
BMC Plant Biol ; 24(1): 447, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38783192

RESUMEN

BACKGROUND: Amino acids are not only the main form of N in rice, but also are vital for its growth and development. These processes are facilitated by amino acid transporters within the plant. Despite their significance, only a few AAP amino acid transporters have been reported. RESULTS: In this study, we observed that there were differences in the expression of amino acid transporter OsAAP7 among 521 wild cultivated rice varieties, and it directly negatively correlated with tillering and grain yield per plant. We revealed that OsAAP7 protein was localized to the endoplasmic reticulum and had absorption and transport affinity for amino acids such as phenylalanine (Phe), lysine (Lys), leucine (Leu), and arginine (Arg) using subcellular localization, yeast substrate testing, fluorescent amino acid uptake, and amino acid content determination. Further hydroponic studies showed that exogenous application of amino acids Phe, Lys and Arg inhibited the growth of axillary buds in the overexpression lines, and promoted the elongation of axillary buds in the mutant lines. Finally, RNA-seq analysis showed that the expression patterns of genes related to nitrogen, auxin and cytokinin pathways were changed in axillary buds of OsAAP7 transgenic plants. CONCLUSIONS: This study revealed the gene function of OsAAP7, and found that blocking of amino acid transporter OsAAP7 with CRISPR/Cas9 technology promoted tillering and yield by determining basic and neutral amino acids accumulation in rice.


Asunto(s)
Oryza , Proteínas de Plantas , Oryza/genética , Oryza/metabolismo , Oryza/crecimiento & desarrollo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Sistemas de Transporte de Aminoácidos/metabolismo , Sistemas de Transporte de Aminoácidos/genética , Plantas Modificadas Genéticamente , Aminoácidos Neutros/metabolismo , Regulación de la Expresión Génica de las Plantas , Aminoácidos/metabolismo
8.
Cell Mol Biol (Noisy-le-grand) ; 70(3): 136-141, 2024 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-38650143

RESUMEN

This study aimed to explore the core genes of craniopharyngioma angiogenesis for targeted vascular therapy based on single-cell nuclear transcriptome sequencing. For single-cell nuclear transcriptome sequencing, we collected six samples from the tumor center and adjacent hypothalamic tumor tissues from three patients with craniopharyngioma, as well as four normal brain tissues based on Gene Expression Omnibus. We screened genes with differential up-regulation between vascular endothelial cells of craniopharyngioma and those of normal brain tissues, performed GO and KEGG analysis, constructed the protein-protein interaction network, and selected key genes verified using immunofluorescence. After data cleaning and quality control, 623 craniopharyngioma endothelial cells and 439 healthy brain endothelial cells were obtained. Compared with normal brain endothelial cells, craniopharyngioma endothelial cells were screened for 394 differentially up-expressed genes (DEGs). GO and KEGG results showed that DEGs probably modulated endothelial cells, adherens junction, focal adhesion, migration, actin cytoskeleton, and invasion via the PI3K-AKT, Rap1, Ras, Wnt, and Hippo pathways. The core genes screened were CTNNB1, PTK2, ITGB1, STAT3, FYN, HIF1A, VCL, SMAD3, PECAM1, FOS, and CDH5. This study obtained possible anti-angiogenic genes in craniopharyngioma. Our results shed novel insights into molecular mechanisms and craniopharyngioma treatment.


Asunto(s)
Craneofaringioma , Regulación Neoplásica de la Expresión Génica , Neovascularización Patológica , Análisis de la Célula Individual , Transcriptoma , Humanos , Craneofaringioma/genética , Craneofaringioma/patología , Craneofaringioma/metabolismo , Neovascularización Patológica/genética , Análisis de la Célula Individual/métodos , Transcriptoma/genética , Perfilación de la Expresión Génica/métodos , Mapas de Interacción de Proteínas/genética , Neoplasias Hipofisarias/genética , Neoplasias Hipofisarias/patología , Neoplasias Hipofisarias/irrigación sanguínea , Neoplasias Hipofisarias/metabolismo , Células Endoteliales/metabolismo , Células Endoteliales/patología , Redes Reguladoras de Genes , Angiogénesis
9.
J Hazard Mater ; 470: 134178, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38608581

RESUMEN

Triclocarban (TCC), an emerging organic contaminant, poses a potential threat to human health with long-term exposure. Here, Rhodococcus rhodochrous BX2 and Pseudomonas sp. LY-1 were utilized to degrade TCC at environmental related concentrations for enhancing TCC biodegradation and investigating whether the toxicity of intermediate metabolites is lower than that of the parent compound. The results demonstrated that the bacterial consortium could degrade TCC by 82.0% within 7 days. The calculated 96 h LC50 for TCC, as well as its main degradation product 3,4-Dichloroaniline (DCA) were 0.134 mg/L and 1.318 mg/L respectively. Biodegradation also alleviated histopathological lesions induced by TCC in zebrafish liver and gut tissues. Liver transcriptome analysis revealed that biodegradation weakened differential expression of genes involved in disrupted immune regulation and lipid metabolism caused by TCC, verified through RT-qPCR analysis and measurement of related enzyme activities and protein contents. 16 S rRNA sequencing indicated that exposure to TCC led to gut microbial dysbiosis, which was efficiently improved through TCC biodegradation, resulting in decreased relative abundances of major pathogens. Overall, this study evaluated potential environmental risks associated with biodegradation of TCC and explored possible biodetoxification mechanisms, providing a theoretical foundation for efficient and harmless bioremediation of environmental pollutants.


Asunto(s)
Biodegradación Ambiental , Carbanilidas , Microbioma Gastrointestinal , Hígado , Pseudomonas , Rhodococcus , Pez Cebra , Animales , Carbanilidas/toxicidad , Hígado/metabolismo , Hígado/efectos de los fármacos , Microbioma Gastrointestinal/efectos de los fármacos , Rhodococcus/metabolismo , Pseudomonas/metabolismo , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/metabolismo , Consorcios Microbianos/efectos de los fármacos , Compuestos de Anilina/toxicidad , Compuestos de Anilina/metabolismo , Inactivación Metabólica
10.
Physiol Plant ; 176(2): e14229, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38413386

RESUMEN

Kam Sweet Rice is a high-quality local variety of Guizhou province in China, but most varieties have awns on lemma. In this study, we aimed to obtain awnless varieties of Kam Sweet Rice by blocking the awn development-related gene OsGAD1 using CRISPR/Cas9 technology. We determined that natural variations of the OsGAD1 triggered different lengths of awns of Kam Sweet Rice. We found that the awning rate of the CRISPR lines of OsGAD1 in Guxiangnuo, Goujingao and Gouhuanggang decreased by over 65%, and the number of grains per panicle and yield per plant increased by more than 17% and 20% compared to the wild-types. Furthermore, we indicated that blocking OsGAD1 resulted in an increase of over 2% in the brown rice rate and milled rice rate in these varieties. In addition, the analysis of the transcriptome revealed that the regulation of awn development and yield formation in CRISPR lines of OsGAD1 may involve genes associated with phytohormone and nitrogen pathways. These results suggest that blocking OsGAD1 in Kam Sweet Rice using CRISPR/Cas9 technology can be used for breeding programs seeking high yield and grain quality of Kam Sweet Rice.


Asunto(s)
Oryza , Oryza/metabolismo , Grano Comestible/genética , Alelos , China
11.
Ultrason Sonochem ; 103: 106786, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38309049

RESUMEN

To maximally maintain fruits and vegetables quality after harvest, this study used ultrasonic (US) and ultra-high pressure (UHP) techniques as pretreatments for radio frequency vacuum (RFV) drying of peach slices, and investigated the effects of different pretreatments (US, UHP, UHP-US, and US-UHP) on drying characteristics, physicochemical qualities, texture properties, and sensory evaluation of peach slices. Results showed that the drying rate was increased by 15.79 âˆ¼ 54.39 % and the contents of pectin, hemicellulose, total phenolic, total flavonoid, phenolic acids, individual sugar annd antioxidant of the samples were significantly increased after US combined with UHP pretreatment (P < 0.05). US-UHP + RFV dried peach slices obtained brighter color, better texture attributes of hardness, cohesiveness, chewiness, springiness, and resilience. The dehydrated samples pretreated by UHP-US had the best overall acceptance, appearance, and crispness with lower off-odor and sourness compared to the dehydrated peach slices with US and UHP pretreatment. Notably, the highest cellulose and organic acids were found in dehydrated peach slices by control, followed by samples US, and samples with UHP pretreatment. The microstructure showed that the internal organization of peach slices appeared as uniform and regular honeycomb porous structure after US-UHP pretreatment. The findings may provide theoretical reference for the development of energy-efficient and high-quality drying technology for fruits and vegetables.


Asunto(s)
Prunus persica , Vacio , Desecación/métodos , Antioxidantes/química , Fenoles/análisis
12.
JCI Insight ; 9(5)2024 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-38329813

RESUMEN

The human adult immune system maintains normal T cell counts and compensates for T cell loss throughout life, mainly through peripheral homeostatic proliferation after the ability of the thymus to generate new T cells has rapidly declined at adolescence. This process is mainly driven by STAT5-activating cytokines, most importantly IL-7, and is very effective in maintaining a large naive CD4+ T cell compartment into older age. Here, we describe that naive CD4+ T cells undergo adaptations to optimize IL-7 responses by upregulating the guanine-nucleotide exchange factor PREX1 in older age. PREX1 promotes nuclear translocation of phosphorylated STAT5, thereby supporting homeostatic proliferation in response to IL-7. Through the same mechanism, increased expression of PREX1 also biases naive cells to differentiate into effector T cells. These findings are consistent with the concept that primarily beneficial adaptations during aging, i.e., improved homeostasis, account for unfavorable functions of the aged immune system, in this case biased differentiation.


Asunto(s)
Linfocitos T CD4-Positivos , Factor de Transcripción STAT5 , Adulto , Humanos , Anciano , Factor de Transcripción STAT5/metabolismo , Interleucina-7/metabolismo , Proliferación Celular , Homeostasis , Factores de Intercambio de Guanina Nucleótido/metabolismo
13.
Diabetes Metab Syndr Obes ; 17: 203-212, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38222033

RESUMEN

Purpose: Amino acids are the important metabolites in the body and play a crucial role in biological processes. The purpose of this study is to provide a profile of amino acids change in the serum of T2DM patients and identify potential biomarkers. Patients and Methods: In this study, we quantitatively determined the serum amino acid profiles of 30 T2DM patients and 30 healthy volunteers. T test and multivariate statistical analysis were used to identify candidate biomarkers with GraphPad Prism 9.5 software and MetaboAnalyst 5.0 on-line platform. Results: Thirty-four amino acids were quantified, and 19 amino acid levels differed significantly between T2DM and Healthy groups. Screened by the specific screening criteria (VIP>1.0; P<0.05; FC>1.5, or FC<0.67) in MetaboAnalyst 5.0 platform, 8 amino acids were identified as potential biomarkers. Pearson rank correlation test showed 14 differential amino acids were significantly correlated with T2DM-related physiological parameters. Conclusion: The results of this study provide theoretical basis for the subsequent development of dietary supplements for the prevention or treatment of T2DM and its complications.

14.
Eur J Med Chem ; 265: 116118, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38181651

RESUMEN

In this work, we utilized the molecular hybridization strategy to design and synthesize novel 1,2,3-triazole benzothiazole derivatives K1-26. The antiproliferative activities against MGC-803, Kyse30 and HCT-116 cells were explored, and their structure-activity relationship were preliminarily conducted and summarized. Among them, compound K18, exhibited the strongest proliferation inhibitory activity, with esophageal cancer cells Kyse30 and EC-109 being the most sensitive to its effects (IC50 values were 0.042 and 0.038 µM, respectively). Compound K18 effectively inhibited tubulin polymerization (IC50 = 0.446 µM), thereby hindering tubulin polymerize into filamentous microtubules in Kyse30 and EC-109 cells. Additionally, compound K18 induced the degradation of oncogenic protein YAP via the UPS pathway. Based on these dual molecular-level effects, compound K18 could induce G2/M phase arrest and cell apoptosis in Kyse30 and EC-109 cells, as well as regulate the expression levels of cell cycle and apoptosis-related proteins. In summary, our findings highlight a novel 1,2,3-triazole benzothiazole derivative K18, which possesses significant potential for treating esophageal cancers.


Asunto(s)
Antineoplásicos , Neoplasias Esofágicas , Melfalán , gammaglobulinas , Humanos , Moduladores de Tubulina , Tubulina (Proteína)/metabolismo , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Proliferación Celular , Relación Estructura-Actividad , Benzotiazoles/farmacología , Triazoles/farmacología , Neoplasias Esofágicas/tratamiento farmacológico , Polimerizacion , Estructura Molecular
15.
Am J Ophthalmol ; 258: 196-207, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37879454

RESUMEN

PURPOSE: This study seeks to evaluate the ability of the updated stress strain index (SSIv2) and other Corvis ST biomechanical parameters in distinguishing between keratoconus at different disease stages and normal eyes. DESIGN: Diagnostic accuracy analysis to distinguish disease stages. METHODS: 1084 eyes were included and divided into groups of normal (199 eyes), forme fruste keratoconus (FFKC, 194 eyes), subclinical keratoconus (SKC, 113 eyes), mild clinical keratoconus (CKC-Ⅰ, 175 eyes), moderate clinical keratoconus (CKC-Ⅱ, 204 eyes), and severe clinical keratoconus (CKC-Ⅲ, 199 eyes). Each eye was subjected to a Corvis ST examination to determine the central corneal thickness (CCT), biomechanically corrected intraocular pressure (bIOP), SSIv2 (updated stress-strain index), and other 8 Corvis parameters including the stress-strain index (SSIv1), stiffness parameter at first applanation (SP-A1), first applanation time (A1T), Ambrósio relational thickness to the horizontal profile (ARTh), integrated inverse radius (IIR), maximum deformation amplitude (DAM), ratio between deformation amplitude at the apex and at 2 mm nasal and temporal (DARatio2), and Corvis biomechanical index (CBI). The sensitivity and specificity of these parameters in diagnosing keratoconus were analyzed through receiver operating characteristic curves. RESULTS: Before and after correction for CCT and bIOP, SSIv2 and ARTh were significantly higher and IIR and CBI were significantly lower in the normal group than in the FFKC group, SKC group and the 3 CKC groups (all P < .05). There were also significant correlations between the values of SSIv2, ARTh, IIR, CBI, and the CKC severity (all P < .05). AUC of SSIv2 was significantly higher than all other Corvis parameters in distinguishing normal eyes from FFKC, followed by IIR, ARTh and CBI. CONCLUSION: Corvis ST's updated stress-strain index, SSIv2, demonstrated superior performance in differentiating between normal and keratoconic corneas, and between corneas with different keratoconus stages. Similar, but less pronounced, performance was demonstrated by the IIR, ARTh and CBI.


Asunto(s)
Queratocono , Humanos , Queratocono/diagnóstico , Topografía de la Córnea , Córnea , Tonometría Ocular , Presión Intraocular , Curva ROC , Fenómenos Biomecánicos
16.
BMC Pharmacol Toxicol ; 24(1): 50, 2023 10 12.
Artículo en Inglés | MEDLINE | ID: mdl-37828612

RESUMEN

Chemotherapy resistance hinders the successful treatment of osteosarcoma (OS) to some extent. Previous studies have confirmed that metformin (Met) enhances apoptosis induced by chemotherapeutic drugs, but the underlying mechanism remains unclear. To establish adriamycin (ADM)-resistant MG-63 (MG-63/ADM) cells, the dosage of ADM was progressively increased. The results of qRT-PCR and Western blotting demonstrated that the expression level of Yin Yang 1 (YY1) and multi-drug resistance-1 (MDR1) in MG-63/ADM cells were remarkably increased compared with those in MG-63 cells. Met dramatically enhanced ADM cytotoxicity and accelerated apoptosis of MG-63/ADM cells. Moreover, Met suppressed the expressions of YY1 and MDR1 in MG-63/ADM cells. YY1 promoted its transcriptional expression by directly binding to the MDR1 promoter. Furthermore, the effects of Met on ADM sensitivity in MG-63/ADM cells was reversed due to overexpression of YY1 or MDR1. Collectively, these findings suggested that Met inhibited YY1/MDR1 pathway to reverse ADM resistance in OS, providing a new insight into the mechanism of Met in ADM resistance of OS.


Asunto(s)
Doxorrubicina , Osteosarcoma , Humanos , Doxorrubicina/farmacología , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Resistencia a Antineoplásicos/genética , Resistencia a Múltiples Medicamentos/genética , Apoptosis , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/genética , Línea Celular Tumoral , Factor de Transcripción YY1/genética , Factor de Transcripción YY1/metabolismo
17.
Angew Chem Int Ed Engl ; 62(43): e202309319, 2023 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-37673793

RESUMEN

Electroreduction of CO2 to multi-carbon (C2+ ) products is a promising approach for utilization of renewable energy, in which the interfacial water quantity is critical for both the C2+ product selectivity and the stability of Cu-based electrocatalytic sites. Functionalization of long-chain alkyl molecules on a catalyst surface can help to increase its stability, while it also tends to block the transport of water, thus inhibiting the C2+ product formation. Herein, we demonstrate the fine tuning of interfacial water by surface assembly of toluene on Cu nanosheets, allowing for sustained and enriched CO2 supply but retarded water transfer to catalytic surface. Compared to bare Cu with fast cathodic corrosion and long-chain alkyl-modified Cu with main CO product, the toluene assembly on Cu nanosheet surface enabled a high Faradaic efficiency of 78 % for C2+ and a partial current density of 1.81 A cm-2 . The toluene-modified Cu catalyst further exhibited highly stable CO2 -to-C2 H4 conversion of 400 h in a membrane-electrode-assembly electrolyzer, suggesting the attractive feature for both efficient C2+ selectivity and excellent stability.

18.
STAR Protoc ; 4(4): 102515, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-37742179

RESUMEN

Plasma extracellular vesicles (EVs) represent a potential resource for biomarkers of multiple diseases. Here, we present a protocol for obtaining EVs from human plasma using asymmetrical flow field-flow fractionation technology. We describe steps for using tandem mass tags to perform comparative proteomic studies of a large clinical cohort. We then detail targeted quantitative analysis of differential proteins based on a parallel reaction monitoring technique. For complete details on the use and execution of this protocol, please refer to Wu et al. (2020)1 and Li et al. (2023).2.


Asunto(s)
Vesículas Extracelulares , Fraccionamiento de Campo-Flujo , Humanos , Proteómica , Tecnología
19.
Cancer Biol Med ; 2023 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-37589244

RESUMEN

Gastric cancer (GC), the fifth most common cancer globally, remains the leading cause of cancer deaths worldwide. Inflammation-induced tumorigenesis is the predominant process in GC development; therefore, systematic research in this area should improve understanding of the biological mechanisms that initiate GC development and promote cancer hallmarks. Here, we summarize biological knowledge regarding gastric inflammation-induced tumorigenesis, and characterize the multi-omics data and systems biology methods for investigating GC development. Of note, we highlight pioneering studies in multi-omics data and state-of-the-art network-based algorithms used for dissecting the features of gastric inflammation-induced tumorigenesis, and we propose translational applications in early GC warning biomarkers and precise treatment strategies. This review offers integrative insights for GC research, with the goal of paving the way to novel paradigms for GC precision oncology and prevention.

20.
J Neurochem ; 166(2): 265-279, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37263975

RESUMEN

Studies of the intracranial vasculature in patients with ischemic stroke caused by atherosclerosis (AS) and cardiac embolism have revealed significantly different degrees of AS, plaque, and vascular stenosis. And the endothelium has a great influence on the vasculature throughout the circulatory system, especially in the brain. This study aimed to investigate the mechanistic differences in endothelial injury between atrial fibrillation (AF)- and AS-induced ischemic stroke. All target genes of AF, AS, and the vascular endothelial cell (VC) were obtained from the GeneCards database; the differential genes of AF and AS separately associated with the VC were established by a Venn diagram. A protein-protein interaction network was created, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases were used to perform genomic enrichment and functional enrichment analysis. Hub genes were selected by Maximal Clique Centrality algorithm ranking and correlation linkage in the STRING database, and then, clinical serum samples were used to verify the quantitative expressions in the AF, AF stroke, AS, and AS stroke groups. Fifty-five AF-VC-related genes and ninety-three AS-VC-related genes were screened, which differed in biological function, cellular composition, and molecular function. The genes correlation between AF and vascular endothelial cells (VCs) was KRAS and PTPN11, and those correlation between AS and VCs was IL-4, IFNG, IL-17A, and CSF-2. IL-4 and CSF-2 may be relevant proteins involved in the differences in stroke mechanisms between AF and AS, and they may act by further influencing the function of their downstream cells. This study provides a preliminary theoretical basis for investigating the differences in mechanisms of endothelial injury between AF- and AS-induced ischemic stroke.


Asunto(s)
Aterosclerosis , Fibrilación Atrial , Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Fibrilación Atrial/genética , Fibrilación Atrial/complicaciones , Factor Estimulante de Colonias de Granulocitos y Macrófagos , Isquemia Encefálica/genética , Isquemia Encefálica/complicaciones , Células Endoteliales , Interleucina-4 , Factores de Riesgo , Accidente Cerebrovascular/genética , Accidente Cerebrovascular/complicaciones , Aterosclerosis/genética , Aterosclerosis/complicaciones , Biología Computacional , Endotelio
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