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1.
Semin Ophthalmol ; : 1-12, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38949222

RESUMEN

OBJECTIVE: To dynamically track the publications on central serous chorioretinopathy (CSC) and depict the research status and hot spots to guide future research. METHODS: Gather all papers published in this area between 2004 and 2024 in the WOSCC databases comprehensively, assess their trends, and characterize the contributions of various nations, authors, institutions, and journals. In addition, VOSviewer, CiteSpace, and R software are used to obtain the most popular keywords for the topic. RESULTS: A total of 2,203 papers were published across 1,863 institutions in 59 countries. Among these, 6,907 authors contributed to publications in 300 journals and generated a total of 35,638 citations. The number of publications continues to grow steadily. Notably, Jay Chhablani's team/Lab stands out as the leading contributor with ownership of 84 publications. Through keyword network analysis and clustering techniques, risk factor-related clustering, imaging-related clustering, pathogenesis-related clustering, and treatment-related clustering were identified. Furthermore, keyword analysis has unveiled emerging frontier areas including pachychoroid disease, choroidal vasculature abnormalities, PDT therapy, and optical coherence tomography that have garnered increasing interest. CONCLUSION: This study presents a comprehensive review of central serous retinopathy research conducted in the past two decades, highlighting key trends and exploring emerging research frontiers within this field. As such, it provides valuable references and suggestions for researchers engaged in studying this topic.

2.
RSC Adv ; 14(29): 20479-20491, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38946769

RESUMEN

Environment-friendly and biodegradable packaging materials have attracted widespread attention. Development of green solutions to extend the fruit shelf life and address fruit preservation thus has a far-reaching impact. In this study, high-barrier white cardboard (WC) was prepared by a facile coating method. Compared with the WC substrate, the WVP value of the polyvinylidene chloride (PVDC) emulsion-coated WC (3.46 × 10-11 g m m-2 s-1 kPa-1) decreased 73.8% and the OP value (14.8 cm3 m-2 day-1·Pa-1) decreased 61.9%. In addition, the mechanical properties of the PVDC emulsion-coated WC increased significantly. The weight loss rate and decay rate of the stored fruits packaged with PVDC emulsion-coated WC decreased by about 5%. The high barrier PVDC emulsion-coated WC with excellent mechanical properties, good barrier effect, and preservation function was successfully prepared. Benefitting from these investigated characteristics, the obtained coated WC can be used to package fruits to reduce water loss and delay ripening, and thus extend their shelf life, exhibiting a favorable effect on blueberry and grape storage. Overall, the fabricated eco-friendly coated white cardboard has shown great potential for biodegradable packaging applications. We believe the current work presents an approach to address perishable fruit preservation and provide a supplement alternative.

3.
Heliyon ; 10(12): e32596, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38975185

RESUMEN

Objective: This study aims to examine the trends in machine learning application to meningiomas between 2004 and 2023. Methods: Publication data were extracted from the Science Citation Index Expanded (SCI-E) within the Web of Science Core Collection (WOSCC). Using CiteSpace 6.2.R6, a comprehensive analysis of publications, authors, cited authors, countries, institutions, cited journals, references, and keywords was conducted on December 1, 2023. Results: The analysis included a total of 342 articles. Prior to 2007, no publications existed in this field, and the number remained modest until 2017. A significant increase occurred in publications from 2018 onwards. The majority of the top 10 authors hailed from Germany and China, with the USA also exerting substantial international influence, particularly in academic institutions. Journals from the IEEE series contributed significantly to the publications. "Deep learning," "brain tumor," and "classification" emerged as the primary keywords of focus among researchers. The developmental pattern in this field primarily involved a combination of interdisciplinary integration and the refinement of major disciplinary branches. Conclusion: Machine learning has demonstrated significant value in predicting early meningiomas and tailoring treatment plans. Key research focuses involve optimizing detection indicators and selecting superior machine learning algorithms. Future efforts should aim to develop high-performance algorithms to drive further innovation in this field.

4.
Acta Trop ; : 107320, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-39002739

RESUMEN

PURPOSE: The polarization of macrophages with the resulting inflammatory response play a crucial part in tissue and organ damage due to inflammatory. Study has proved Lian Hua Qing Wen capsules (LHQW) can reduce activation of inflammatory response and damage of tissue derived from the inflammatory reactions. However, the mechanism of LHQW regulates the macrophage-induced inflammatory response is unclear. Therefore, we investigated the mechanism of LHQW regulated the inflammatory response of M1 macrophages by cellular experiments and computer simulations. METHODS: This study has analysed the targets and mechanisms of macrophage regulating inflammatory response at gene and protein levels through bioinformatics. The monomeric components of LHQW were analyzed by High Performance Liquid Chromatography (HPLC). We established the in vitro cell model by M1 macrophages (Induction of THP-1 cells into M1 macrophages). RT-qPCR and immunofluorescence were used to detect changes in gene and protein levels of key targets after LHQW treatment. Computer simulations were utilized to verify the binding stability of monomeric components and protein targets. RESULTS: Macrophages had 140690 gene targets, inflammatory response had 12192 gene targets, intersection gene targets were 11772. Key monomeric components (including: Pinocembrin, Fargesone-A, Nodakenin and Bowdichione) of LHQW were screened by HPLC. The results of cellular experiments indicated that LHQW could significantly reduce the mRNA expression of CCR5, CSF2, IFNG and TNF, thereby alleviating the inflammatory response caused by M1 macrophage. The computer simulations further validated the binding stability and conformation of key monomeric components and key protein targets, and IFNG/Nodakenin was able to form the most stable binding conformation for its action. CONCLUSION: In this study, the mechanism of LHQW inhibits the polarization of macrophages and the resulting inflammatory response was investigated by computer simulations and cellular experiments. We found that LHQW may not only reduce cell damage and death by acting on TNF and CCR5, but also inhibit the immune recognition process and inflammatory response by regulating CSF2 and IFNG to prevent polarization of macrophages. Therefore, these results suggested that LHQW may act through multiple targets to inhibit the polarization of macrophages and the resulting inflammatory response.

5.
Molecules ; 29(13)2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38999081

RESUMEN

Abscisic acid (ABA) is one of the many naturally occurring phytohormones widely found in plants. This study focused on refining APAn, a series of previously developed agonism/antagonism switching probes. Twelve novel APAn analogues were synthesized by introducing varied branched or oxygen-containing chains at the C-6' position, and these were screened. Through germination assays conducted on A. thaliana, colza, and rice seeds, as well as investigations into stomatal movement, several highly active ABA receptor antagonists were identified. Microscale thermophoresis (MST) assays, molecular docking, and molecular dynamics simulation showed that they had stronger receptor affinity than ABA, while PP2C phosphatase assays indicated that the C-6'-tail chain extending from the 3' channel effectively prevented the ligand-receptor binary complex from binding to PP2C phosphatase, demonstrating strong antagonistic activity. These antagonists showed effective potential in promoting seed germination and stomatal opening of plants exposed to abiotic stress, particularly cold and salt stress, offering advantages for cultivating crops under adverse conditions. Moreover, their combined application with fluridone and gibberellic acid could provide more practical agricultural solutions, presenting new insights and tools for overcoming agricultural challenges.


Asunto(s)
Ácido Abscísico , Germinación , Simulación del Acoplamiento Molecular , Ácido Abscísico/química , Germinación/efectos de los fármacos , Arabidopsis/efectos de los fármacos , Arabidopsis/metabolismo , Reguladores del Crecimiento de las Plantas/química , Reguladores del Crecimiento de las Plantas/farmacología , Semillas/efectos de los fármacos , Semillas/química , Semillas/crecimiento & desarrollo , Oryza/efectos de los fármacos , Oryza/metabolismo , Oryza/crecimiento & desarrollo , Proteínas de Arabidopsis/antagonistas & inhibidores , Proteínas de Arabidopsis/metabolismo , Simulación de Dinámica Molecular , Agricultura/métodos , Giberelinas/química , Giberelinas/metabolismo , Piridonas
6.
Proc Natl Acad Sci U S A ; 121(28): e2404062121, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38968109

RESUMEN

Nutrient sensing and adaptation in the placenta are essential for pregnancy viability and proper fetal growth. Our recent study demonstrated that the placenta adapts to nutrient insufficiency through mechanistic target of rapamycin (mTOR) inhibition-mediated trophoblast differentiation toward syncytiotrophoblasts (STBs), a highly specialized multinucleated trophoblast subtype mediating extensive maternal-fetal interactions. However, the underlying mechanism remains elusive. Here, we unravel the indispensable role of the mTORC1 downstream transcriptional factor TFEB in STB formation both in vitro and in vivo. TFEB deficiency significantly impaired STB differentiation in human trophoblasts and placenta organoids. Consistently, systemic or trophoblast-specific deletion of Tfeb compromised STB formation and placental vascular construction, leading to severe embryonic lethality. Mechanistically, TFEB conferred direct transcriptional activation of the fusogen ERVFRD-1 in human trophoblasts and thereby promoted STB formation, independent of its canonical function as a master regulator of the autophagy-lysosomal pathway. Moreover, we demonstrated that TFEB directed the trophoblast syncytialization response driven by mTOR complex 1 (mTORC1) signaling. TFEB expression positively correlated with the reinforced trophoblast syncytialization in human fetal growth-restricted placentas exhibiting suppressed mTORC1 activity. Our findings substantiate that the TFEB-fusogen axis ensures proper STB formation during placenta development and under nutrient stress, shedding light on TFEB as a mechanistic link between nutrient-sensing machinery and trophoblast differentiation.


Asunto(s)
Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Diferenciación Celular , Diana Mecanicista del Complejo 1 de la Rapamicina , Trofoblastos , Trofoblastos/metabolismo , Humanos , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Femenino , Embarazo , Ratones , Animales , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Placenta/metabolismo , Transducción de Señal , Autofagia/fisiología
7.
Sci Rep ; 14(1): 14755, 2024 06 26.
Artículo en Inglés | MEDLINE | ID: mdl-38926437

RESUMEN

Streptococcus gallolyticus (Sg) is a non-motile, gram-positive bacterium that causes infective endocarditis (inflammation of the heart lining). Because Sg has gained resistance to existing antibiotics and there is currently no drug available, developing effective anti-Sg drugs is critical. This study combined core proteomics with a subtractive proteomics technique to identify potential therapeutic targets for Sg. Several bioinformatics approaches were used to eliminate non-essential and human-specific homologous sequences from the bacterial proteome. Then, virulence, druggability, subcellular localization, and functional analyses were carried out to specify the participation of significant bacterial proteins in various cellular processes. The pathogen's genome contained three druggable proteins, glucosamine-1phosphate N-acetyltransferase (GlmU), RNA polymerase sigma factor (RpoD), and pantetheine-phosphate adenylyltransferase (PPAT) which could serve as effective targets for developing novel drugs. 3D structures of target protein were modeled through Swiss Model. A natural product library containing 10,000 molecules from the LOTUS database was docked against therapeutic target proteins. Following an evaluation of the docking results using the glide gscore, the top 10 compounds docked against each protein receptor were chosen. LTS001632, LTS0243441, and LTS0236112 were the compounds that exhibited the highest binding affinities against GlmU, PPAT, and RpoD, respectively, among the compounds that were chosen. To augment the docking data, molecular dynamics simulations and MM-GBSA binding free energy were also utilized. More in-vitro research is necessary to transform these possible inhibitors into therapeutic drugs, though computer validations were employed in this study. This combination of computational techniques paves the way for targeted antibiotic development, which addresses the critical need for new therapeutic strategies against S. gallolyticus infections.


Asunto(s)
Antibacterianos , Proteínas Bacterianas , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Proteómica , Streptococcus gallolyticus , Proteómica/métodos , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/química , Proteínas Bacterianas/antagonistas & inhibidores , Antibacterianos/farmacología , Antibacterianos/química , Streptococcus gallolyticus/metabolismo , Humanos
8.
J Environ Manage ; 365: 121523, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38901321

RESUMEN

Anaerobic oxidation of methane (AOM) is a microbial process of importance in the global carbon cycle. AOM is predominantly mediated by anaerobic methanotrophic archaea (ANME), the physiology of which is still poorly understood. Here we present a new addition to the current physiological understanding of ANME by examining, for the first time, the biochemical and redox-active properties of the extracellular polymeric substances (EPS) of an ANME enrichment culture. Using a 'Candidatus Methanoperedens nitroreducens'-dominated methanotrophic consortium as the representative, we found it can produce an EPS matrix featuring a high protein-to-polysaccharide ratio of ∼8. Characterization of EPS using FTIR revealed the dominance of protein-associated amide I and amide II bands in the EPS. XPS characterization revealed the functional group of C-(O/N) from proteins accounted for 63.7% of total carbon. Heme-reactive staining and spectroscopic characterization confirmed the distribution of c-type cytochromes in this protein-dominated EPS, which potentially enabled its electroactive characteristic. Redox-active c-type cytochromes in EPS mediated the EET of 'Ca. M. nitroreducens' for the reduction of Ag+ to metallic Ag, which was confirmed by both ex-situ experiments with extracted soluble EPS and in-situ experiments with pristine EPS matrix surrounding cells. The formation of nanoparticles in the EPS matrix during in-situ extracellular Ag + reduction resulted in a relatively lower intracellular Ag distribution fraction, beneficial for alleviating the Ag toxicity to cells. The results of this study provide the first biochemical information on EPS of anaerobic methanotrophic consortia and a new insight into its physiological role in AOM process.


Asunto(s)
Matriz Extracelular de Sustancias Poliméricas , Metano , Oxidación-Reducción , Metano/metabolismo , Matriz Extracelular de Sustancias Poliméricas/metabolismo , Anaerobiosis , Archaea/metabolismo
9.
Comput Biol Med ; 178: 108714, 2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38889627

RESUMEN

BACKGROUND: The emergence of digital whole slide image (WSI) has driven the development of computational pathology. However, obtaining patch-level annotations is challenging and time-consuming due to the high resolution of WSI, which limits the applicability of fully supervised methods. We aim to address the challenges related to patch-level annotations. METHODS: We propose a universal framework for weakly supervised WSI analysis based on Multiple Instance Learning (MIL). To achieve effective aggregation of instance features, we design a feature aggregation module from multiple dimensions by considering feature distribution, instances correlation and instance-level evaluation. First, we implement instance-level standardization layer and deep projection unit to improve the separation of instances in the feature space. Then, a self-attention mechanism is employed to explore dependencies between instances. Additionally, an instance-level pseudo-label evaluation method is introduced to enhance the available information during the weak supervision process. Finally, a bag-level classifier is used to obtain preliminary WSI classification results. To achieve even more accurate WSI label predictions, we have designed a key instance selection module that strengthens the learning of local features for instances. Combining the results from both modules leads to an improvement in WSI prediction accuracy. RESULTS: Experiments conducted on Camelyon16, TCGA-NSCLC, SICAPv2, PANDA and classical MIL benchmark datasets demonstrate that our proposed method achieves a competitive performance compared to some recent methods, with maximum improvement of 14.6 % in terms of classification accuracy. CONCLUSION: Our method can improve the classification accuracy of whole slide images in a weakly supervised way, and more accurately detect lesion areas.

10.
Int J Biol Macromol ; 270(Pt 1): 132066, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38705323

RESUMEN

A comprehensive multiscale analysis was conducted to explore the effects of different ratios of these materials on its properties. The results show that KC played a crucial role in controlling solution viscosity and gel and sol temperatures. The dissolution time at high water temperatures primarily decreased with an increase in SA content. Higher KC and CS content increased tensile strength (TS) and elongation at break (ε), while also exhibiting better thermal stability. Water vapor transmission (WVT) and permeability (PV) initially decreased, then increased with the increase of SA and CS contents. Finally, an SA:KC:CS ratio of 1:3:2 showed optimal comprehensive properties, with a dissolution time of about 60.0 ± 3.8 s, TS of 23.80 ± 0.29 MPa, ε of 18.61 ± 0.34 %, WVT of 21.74 ± 0.62 g/m2·24h, and PV of 5.39 ± 0.17 meq/kg. Meanwhile, the SA:KC:CS edible food packaging only introduced minimal effects on food after dissolution, and the total bacterial count met regulatory standards.


Asunto(s)
Películas Comestibles , Embalaje de Alimentos , Permeabilidad , Agua , Embalaje de Alimentos/métodos , Agua/química , Polisacáridos/química , Solubilidad , Calor , Viscosidad , Resistencia a la Tracción , Vapor , Fenómenos Mecánicos , Comida Rápida/análisis
11.
Photodiagnosis Photodyn Ther ; 48: 104230, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38821236

RESUMEN

BACKGROUND: Primary membranous nephropathy (PMN) patients may experience retinal microvascular changes. However, current diagnostic methods for PMN are not accurate in analyzing these modifications. In the present study, optical coherence tomography angiography (OCTA) was used for quantitative measurement of microvascular changes in the eyes of PMN patients. METHODS: A total of 26 patients with PMN and 26 healthy control (HC) were evaluated in this cross-sectional study. Optical coherence tomography (OCT) and OCTA were used to collect retinal thickness (RT) and microvascular parameters in the macula and optic disk in the superficial capillary plexus (SCP) of all subjects. Clinical data were collected from the PMN group. The OCT and OCTA data for PMN and HC group were compared, and the correlation between the OCTA and clinical data in the PMN group was determined. RESULTS: Vascular density (VD) and perfusion density (PD) in the macular area of the PMN group were significantly lower than those of the HC group, especially in the temporal quadrant. No significant difference in the foveal avascular zone (FAZ), optic disc microvascular parameters, RT, and retinal nerve fiber layer (RNFL) thickness was observed between the two groups. Correlation was noted between VD and PD in the macular area and clinical indicators, such as serum creatinine, serum urea nitrogen, 24 h urine volume and urinary protein concentration. CONCLUSION: Microvascular alterations in PMN patients occurred before ocular symptoms. The present quantitative study proposed a measurement method for detecting early retinal vascular injury in PMN patients.

12.
Front Neural Circuits ; 18: 1384621, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38736977

RESUMEN

The posterior intralaminar thalamic nucleus (PIL) and peripeduncular nucleus (PP) are two adjoining structures located medioventral to the medial geniculate nucleus. The PIL-PP region plays important roles in auditory fear conditioning and in social, maternal and sexual behaviors. Previous studies often lumped the PIL and PP into single entity, and therefore it is not known if they have common and/or different brain-wide connections. In this study, we investigate brain-wide efferent and afferent projections of the PIL and PP using reliable anterograde and retrograde tracing methods. Both PIL and PP project strongly to lateral, medial and anterior basomedial amygdaloid nuclei, posteroventral striatum (putamen and external globus pallidus), amygdalostriatal transition area, zona incerta, superior and inferior colliculi, and the ectorhinal cortex. However, the PP rather than the PIL send stronger projections to the hypothalamic regions such as preoptic area/nucleus, anterior hypothalamic nucleus, and ventromedial nucleus of hypothalamus. As for the afferent projections, both PIL and PP receive multimodal information from auditory (inferior colliculus, superior olivary nucleus, nucleus of lateral lemniscus, and association auditory cortex), visual (superior colliculus and ectorhinal cortex), somatosensory (gracile and cuneate nuclei), motor (external globus pallidus), and limbic (central amygdaloid nucleus, hypothalamus, and insular cortex) structures. However, the PP rather than PIL receives strong projections from the visual related structures parabigeminal nucleus and ventral lateral geniculate nucleus. Additional results from Cre-dependent viral tracing in mice have also confirmed the main results in rats. Together, the findings in this study would provide new insights into the neural circuits and functional correlation of the PIL and PP.


Asunto(s)
Núcleos Talámicos Intralaminares , Vías Nerviosas , Animales , Ratas , Ratones , Masculino , Vías Nerviosas/fisiología , Núcleos Talámicos Intralaminares/fisiología , Ratones Endogámicos C57BL , Ratas Sprague-Dawley , Femenino
13.
Heliyon ; 10(9): e29364, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38720731

RESUMEN

Background: The Jinchan Yishen Tongluo Formula (JCYSTLF) has the effect of delaying senescence in diabetic kidneys. However, the mechanism is not clear. Purpose: Combination methods to investigate the anti-senescence mechanism of JCYSTLF in diabetic kidneys. Methods: The main compounds of JCYSTLF were characterized by LC-MS/MS, and the anti-senescence targets of JCYSTLF were screened via network analysis. Then, we performed in vivo and in vitro experiments to validate the results. Results: The target profiles of compounds were obtained by LC-MS/MS to characterize the primary function of JCYSTLF. Senescence was identified as a key biological functional module of JCYSTLF in the treatment of DN via constructing compounds-target-biological network analysis. Further analysis of senescence-related targets recognized the HIF-1α/autophagy pathway as the core anti-senescence mechanism of JCYSTLF in diabetic kidneys. Animal experiments showed, in comparison with valsartan, JCYSTLF showed an improvement in urinary albumin and renal pathological damage. JCYSTLF enhanced the ability of diabetic kidneys to clear senescence-related proteins via regulating autophagy confirmed by autophagy inhibitor CQ. However, HIF-1α inhibitor 2-ME weakened the role of JCYSLTF in regulating autophagy in diabetic kidneys. Meanwhile, over-expressed HIF-1α in HK-2 cells decreased the levels of SA-ß-gal, p21 and p53 induced by AGEs. Upregulated HIF-1α could reverse the blocking of autophagy induced by AGEs in HK-2 cells evaluated by ptfLC3. Conclusion: We provided in vitro and in vivo evidence for the anti-senescence role of JCYSTLF in regulating the HIF-1α/autophagy pathway.

14.
Water Res ; 256: 121651, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38657312

RESUMEN

The broader reuse of sewage sludge as a soil fertilizer or conditioner is impeded by the presence of toxic metals. Bioleaching, a process that leverages microbial metabolisms and metabolites for metal extraction, is viewed as an economically and environmentally feasible approach for metal removal. This study presents an innovative bioleaching process based on microbial oxidation of ammonia released from sludge hydrolysis, mediated by a novel acid tolerant ammonia-oxidizing bacteria (AOB), Ca. Nitrosoglobus. Over a span of 1024 days, a laboratory-scale bioleaching reactor processing anaerobically digested (AD) sludge achieved an in-situ pH of 2.5 ± 0.3. This acidic environment facilitated efficient leaching of toxic metals from AD sludge, upgrading its quality from Grade C to Grade A (qualified for unrestricted use), according to both stabilization and contaminants criteria. The improved quality of AD sludge could potentially reduce sludge disposal expenses and enable a broader reuse of biosolids. Furthermore, this study revealed a pH-dependent total ammonia affinity of Ca. Nitrosoglobus, with a higher affinity constant at pH 3.5 (67.3 ± 20.7 mg N/L) compared to pH 4.5-7.5 (7.6 - 9.6 mg N/L). This finding indicates that by optimizing ammonium concentrations, the efficiency of this novel ammonium-based bioleaching process could be significantly increased.


Asunto(s)
Compuestos de Amonio , Reactores Biológicos , Aguas del Alcantarillado , Compuestos de Amonio/metabolismo , Amoníaco/metabolismo , Concentración de Iones de Hidrógeno , Metales , Eliminación de Residuos Líquidos/métodos
15.
J Magn Reson Imaging ; 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38647041

RESUMEN

BACKGROUND: Proliferative hepatocellular carcinoma (HCC), aggressive with poor prognosis, and lacks reliable MRI diagnosis. PURPOSE: To develop a diagnostic model for proliferative HCC using liver imaging reporting and data system (LI-RADS) and assess its prognostic value. STUDY TYPE: Retrospective. POPULATION: 241 HCC patients underwent hepatectomy (90 proliferative HCCs: 151 nonproliferative HCCs), divided into the training (N = 167) and validation (N = 74) sets. 57 HCC patients received combination therapy with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). FIELD STRENGTH/SEQUENCE: 3.0 T, T1- and T2-weighted, diffusion-weighted, in- and out-phase, T1 high resolution isotropic volume excitation and dynamic gadoxetic acid-enhanced imaging. ASSESSMENT: LI-RADS v2018 and other MRI features (intratumoral artery, substantial hypoenhancing component, hepatobiliary phase peritumoral hypointensity, and irregular tumor margin) were assessed. A diagnostic model for proliferative HCC was established, stratifying patients into high- and low-risk groups. Follow-up occurred every 3-6 months, and recurrence-free survival (RFS), progression-free survival (PFS) and overall survival (OS) in different groups were compared. STATISTICAL TESTS: Fisher's test or chi-square test, t-test or Mann-Whitney test, logistic regression, Harrell's concordance index (C-index), Kaplan-Meier curves, and Cox proportional hazards. Significance level: P < 0.05. RESULTS: The diagnostic model, incorporating corona enhancement, rim arterial phase hyperenhancement, infiltrative appearance, intratumoral artery, and substantial hypoenhancing component, achieved a C-index of 0.823 (training set) and 0.804 (validation set). Median follow-up was 32.5 months (interquartile range [IQR], 25.1 months) for postsurgery patients, and 16.8 months (IQR: 13.2 months) for combination-treated patients. 99 patients experienced recurrence, and 30 demonstrated tumor nonresponse. Differences were significant in RFS and OS rates between high-risk and low-risk groups post-surgery (40.3% vs. 65.8%, 62.3% vs. 90.1%, at 5 years). In combination-treated patients, PFS rates differed significantly (80.6% vs. 7.7% at 2 years). DATA CONCLUSION: The MR-based model could pre-treatment identify proliferative HCC and assist in prognosis evaluation. TECHNICAL EFFICACY: Stage 2.

16.
Front Immunol ; 15: 1308978, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38571952

RESUMEN

Objective: Acute myocardial infarction (AMI) is a severe cardiovascular disease that threatens human life and health globally. N6-methyladenosine (m6A) governs the fate of RNAs via m6A regulators. Nevertheless, how m6A regulators affect AMI remains to be deciphered. To solve this issue, an integrative analysis of m6A regulators in AMI was conducted. Methods: We acquired transcriptome profiles (GSE59867, GSE48060) of peripheral blood samples from AMI patients and healthy controls. Key m6A regulators were used for LASSO, and consensus clustering was conducted. Next, the m6A score was also computed. Immune cell infiltration, ferroptosis, and oxidative stress were evaluated. In-vitro and in-vivo experiments were conducted to verify the role of the m6A regulator ALKBH5 in AMI. Results: Most m6A regulators presented notable expression alterations in circulating cells of AMI patients versus those of controls. Based on key m6A regulators, we established a gene signature and a nomogram for AMI diagnosis and risk prediction. AMI patients were classified into three m6A clusters or gene clusters, respectively, and each cluster possessed the unique properties of m6A modification, immune cell infiltration, ferroptosis, and oxidative stress. Finally, the m6A score was utilized to quantify m6A modification patterns. Therapeutic targeting of ALKBH5 greatly alleviated apoptosis and intracellular ROS in H/R-induced H9C2 cells and NRCMs. Conclusion: Altogether, our findings highlight the clinical significance of m6A regulators in the diagnosis and risk prediction of AMI and indicate the critical roles of m6A modification in the regulation of immune cell infiltration, ferroptosis, and oxidative stress.


Asunto(s)
Ferroptosis , Infarto del Miocardio , Humanos , Relevancia Clínica , Infarto del Miocardio/genética , Apoptosis/genética , Análisis por Conglomerados , Ferroptosis/genética
17.
J Agric Food Chem ; 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38597654

RESUMEN

Abscisic acid (ABA), a phytohormone, and its analogs have been found to enhance plant resistance to various biotic and abiotic stresses, particularly drought, by activating the ABA signaling pathway. This study used a combination of structure-directed design and molecular docking screening methods to synthesize a novel series of opabactin (OP) analogs. Among them, compounds 4a-4d and 5a showed comparable or superior activity to OP in bioassays, including seed germination and seedling growth inhibition in A. thaliana and rice, stomatal closure, and drought resistance in wheat and soybean. Further transcriptome analysis revealed distinct mechanisms of action between compound 4c and iso-PhABA in enhancing drought tolerance in A. thaliana. These findings highlight the application prospect of 4c and its analogs in agricultural cultivation, particularly in drought resistance. Additionally, they provide new insights into the mechanisms by which different ABA receptor agonists enhance drought resistance.

18.
Opt Express ; 32(4): 5072-5087, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38439243

RESUMEN

The acidic environment is one of the main factors leading to the aging of silicone rubber (SiR) insulators. Aging can reduce the surface hydrophobicity and pollution flashover resistance of insulators, threatening the safe and stable operation of the power grid. Therefore, evaluating the aging state of insulators is essential to prevent flashover accidents on the transmission line. This paper is based on an optical hyperspectral imaging (HSI) technology for pixel-level assessment of insulator aging status. Firstly, the SiR samples were artificially aged in three typical acidic solutions with different concentrations of HNO3, H2SO4, and HCl, and six aging grades of SiR samples were prepared. The HSI of SiR at each aging grade was extracted using a hyperspectral imager. To reduce the calculation complexity and eliminate the interference of useless information in the band, this paper proposes a joint random forest- principal component analysis (RF-PCA) dimensionality reduction method to reduce the original 256-dimensional hyperspectral data to 7 dimensions. Finally, to capture local features in hyperspectral images more effectively and retain the most significant information of the spectral lines, a convolutional neural network (CNN) was used to build a classification model for pixel-level assessment of the SiR's aging state of and visual prediction of insulators' defects. The research method in this paper provides an important guarantee for the timely detection of safety hazards in the power grid.

19.
Biotechnol J ; 19(3): e2300687, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38479994

RESUMEN

Developing an accurate and reliable model for chromatographic separation that meets regulatory requirements and ensures consistency in model development remains challenging. In order to address this challenge, a standardized approach was proposed in this study with ion-exchange chromatography (IEC). The approach includes the following steps: liquid flow identification, system and column-specific parameters determination and validation, multi-component system identification, protein amount validation, steric mass action parameters determination and evaluation, and validation of the calibrated model's generalization ability. The parameter-by-parameter (PbP) calibration method and the consideration of extra-column effects were integrated to enhance the accuracy of the developed models. The experiments designed for implementing the PbP method (five gradient experiments for model calibration and one stepwise experiment for model validation) not only streamline the experimental workload but also ensure the extrapolation abilities of the model. The effectiveness of the standardized approach is successfully validated through an application about the IEC separation of industrial antibody variants, and satisfactory results were observed with R2 ≈ 0.9 for the majority of calibration and validation experiments. The standardized approach proposed in this work contributes significantly to improve the accuracy and reliability of the developed IEC models. Models developed using this standardized approach are ready to be applied to a broader range of industrial separation systems, and are likely find further applications in model-assisted decision-making of process development.


Asunto(s)
Proteínas , Reproducibilidad de los Resultados , Cromatografía por Intercambio Iónico/métodos , Adsorción , Calibración
20.
Open Life Sci ; 19(1): 20220827, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38465334

RESUMEN

Studying the effects of maternal iron deficiency anemia (IDA) is complex owing to its diverse causes, each independently impacting the placenta and fetus. Simple treatment with iron supplements does not always resolve the anemia. Therefore, delving into how IDA alters placental development at a molecular level is crucial to further optimize treatment. This review addresses the effects of IDA on placental structures and functions, including changes in oxygen levels, blood vessels, and the immune system. Profound understanding of physiological characteristics and regulatory mechanisms of placental development is key to explain the mechanisms of abnormal placental development in pregnancy-associated disorders. In turn, future strategies for the prevention and treatment of pregnancy complications involving the placenta can be devised. These studies are significant for improving human reproductive health, enhancing sociodemographic qualities, and even lifelong wellbeing, a focal point in future placental research.

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