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1.
Eur J Radiol ; 181: 111757, 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39326235

RESUMEN

OBJECTIVE: To compare pre-defecation straining without rectal gel and post-defecation straining with the defecation phase, and to investigate their roles in evaluating pelvic organ prolapse (POP). MATERIAL & METHODS: Magnetic Resonance Defecography (MRD) images of 65 patients with a clinical diagnosis of POP were retrospectively reviewed by two independent readers. Measurements were taken at rest, pre-defecation straining without rectal gel, defecation, and post-defecation straining. The presence, sizes, and/or grades of cystocele, uterovaginal prolapse, widened levator hiatus, perineal descent, cul-de-sac hernia, rectocele, and rectal intussusception were evaluated and compared across the four phases. RESULTS: Compared to pre-defecation straining, both defecation and post-defecation straining detected more cases, larger sizes, and higher grades of prolapse in all compartments. When comparing defecation and post-defecation straining, the latter diagnosed four more cases of cystocele (80 % vs 73.9 %, p = 0.2) with larger size (-34.1 vs -29.0, p < 0.01) and higher grade (p = 0.19). Post-defecation straining also identified eight more cases of uterovaginal prolapse (89.2 % vs 73.9 %, p < 0.01) with larger size (-32.9 vs -26.4, p < 0.01) and higher grade (p < 0.01) compared to defecation. Conversely, defecation detected eight more cases of rectocele (46.2 % vs 33.9 %, p < 0.01) with larger size (9.2 vs 6.2 cm, p < 0.01) and higher grade (p = 0.26). CONCLUSION: Post-defecation straining effectively depicts the maximal extent of prolapse in the anterior and middle compartments, and should be performed whenever there is a clinical need for a comprehensive assessment of prolapse in these compartments.

2.
Cancer Commun (Lond) ; 2024 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-39340215

RESUMEN

BACKGROUND: Despite significant strides in lung cancer immunotherapy, the response rates for Kirsten rat sarcoma viral oncogene homolog (KRAS)-driven lung adenocarcinoma (LUAD) patients remain limited. Fibrinogen-like protein 1 (FGL1) is a newly identified immune checkpoint target, and the study of related resistance mechanisms is crucial for improving the treatment outcomes of LUAD patients. This study aimed to elucidate the potential mechanism by which FGL1 regulates the tumor microenvironment in KRAS-mutated cancer. METHODS: The expression levels of FGL1 and SET1 histone methyltransferase (SET1A) in lung cancer were assessed using public databases and clinical samples. Lentiviruses were constructed for transduction to overexpress or silence FGL1 in lung cancer cells and mouse models. The effects of FGL1 and Yes-associated protein (Yap) on the immunoreactivity of cytotoxic T cells in tumor tissues were evaluated using immunofluorescence staining and flow cytometry. Chromatin immunoprecipitation and dual luciferase reporter assays were used to study the SET1A-directed transcriptional program. RESULTS: Upregulation of FGL1 expression in KRAS-mutated cancer was inversely correlated with the infiltration of CD8+ T cells. Mechanistically, KRAS activated extracellular signal-regulated kinase 1/2 (ERK1/2), which subsequently phosphorylated SET1A and increased its stability and nuclear localization. SET1A-mediated methylation of Yap led to Yap sequestration in the nucleus, thereby promoting Yap-induced transcription of FGL1 and immune evasion in KRAS-driven LUAD. Notably, dual blockade of programmed cell death-1 (PD-1) and FGL1 further increased the therapeutic efficacy of anti-PD-1 immunotherapy in LUAD patients. CONCLUSION: FGL1 could be used as a diagnostic biomarker of KRAS-mutated lung cancer, and targeting the Yap-FGL1 axis could increase the efficacy of anti-PD-1 immunotherapy.

3.
Biology (Basel) ; 13(8)2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39194497

RESUMEN

Paediatric obstructive sleep apnoea (OSA) is a highly prevalent sleep disorder resulting in chronic intermittent hypoxia (CIH) that has been linked to metabolism and endocrine impairment. Protein acetylation, which is a frequently occurring posttranslational modification, plays pivotal roles in the regulation of hypothalamic processes. However, the effects of CIH-induced global protein acetylation on hypothalamic function and endocrine metabolism remain poorly understood. To bridge this knowledge gap, we conducted a study utilizing liquid chromatography-mass spectrometry to analyse the lysine acetylome and proteome of the hypothalamus in healthy infantile mice exposed to 3 weeks of intermittent hypoxia (as a CIH model) compared to normoxic mice (as controls). Our analysis identified and quantified 2699 Kac sites in 2453 proteins. These acetylated proteins exhibited disruptions primarily in endocrine metabolism, the citrate cycle (TCA cycle), synapse function, and circadian entrainment. Additionally, we observed significant down-regulation of proteins that are known to be involved in endocrine hormone secretion. This study aimed to elucidate the molecular mechanisms underlying CIH-induced alterations in protein acetylation within the hypothalamus. By providing valuable insights into the pathophysiological processes associated with CIH and their impacts on hypothalamic function, our findings contribute to a deeper understanding of the consequences stemming from CIH-induced changes in protein acetylation within the hypothalamus as well as its potential role in endocrine impairment.

4.
J Neuroinflammation ; 21(1): 208, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39169375

RESUMEN

BACKGROUND: Obstructive sleep apnoea (OSA) is a sleep-disordered breathing characterized by intermittent hypoxia (IH) that may cause cognitive dysfunction. However, the impact of IH on molecular processes involved in cognitive function remains unclear. METHODS: C57BL / 6 J mice were exposed to either normoxia (control) or IH for 6 weeks. DNA hydroxymethylation was quantified by hydroxymethylated DNA immunoprecipitation (hMeDIP) sequencing. ten-eleven translocation 1 (Tet1) was knocked down by lentivirus. Specifically, cognitive function was assessed by behavioral experiments, pathological features were assessed by HE staining, the hippocampal DNA hydroxymethylation was examined by DNA dot blot and immunohistochemical staining, while the Wnt signaling pathway and its downstream effects were studied using qRT-PCR, immunofluorescence staining, and Luminex liquid suspension chip analysis. RESULTS: IH mice showed pathological changes and cognitive dysfunction in the hippocampus. Compared with the control group, IH mice exhibited global DNA hydroxylmethylation in the hippocampus, and the expression of three hydroxylmethylases increased significantly. The Wnt signaling pathway was activated, and the mRNA and 5hmC levels of Wnt3a, Ccnd2, and Prickle2 were significantly up-regulated. Further caused downstream neurogenesis abnormalities and neuroinflammatory activation, manifested as increased expression of IBA1 (a marker of microglia), GFAP (a marker of astrocytes), and DCX (a marker of immature neurons), as well as a range of inflammatory cytokines (e.g. TNFa, IL3, IL9, and IL17A). After Tet1 knocked down, the above indicators return to normal. CONCLUSION: Activation of Wnt signaling pathway by hippocampal Tet1 is associated with cognitive dysfunction induced by IH.


Asunto(s)
Disfunción Cognitiva , Hipocampo , Ratones Endogámicos C57BL , Proteínas Proto-Oncogénicas , Apnea Obstructiva del Sueño , Vía de Señalización Wnt , Animales , Hipocampo/metabolismo , Hipocampo/patología , Ratones , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas/genética , Vía de Señalización Wnt/fisiología , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/patología , Disfunción Cognitiva/etiología , Apnea Obstructiva del Sueño/metabolismo , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/patología , Masculino , Enfermedades Neuroinflamatorias/metabolismo , Enfermedades Neuroinflamatorias/patología , 5-Metilcitosina/análogos & derivados , 5-Metilcitosina/metabolismo , Metilación de ADN , Proteínas de Unión al ADN
5.
Comput Biol Med ; 179: 108843, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39029433

RESUMEN

Respiratory diseases are one of the major health problems worldwide. Early diagnosis of the disease types is of vital importance. As one of the main symptoms of many respiratory diseases, cough may contain information about different pathological changes in the respiratory system. Therefore, many researchers have used cough sounds to diagnose different diseases through artificial intelligence in recent years. The acoustic features and data augmentation methods commonly used in speech tasks are used to achieve better performance. Although these methods are applicable, previous studies have not considered the characteristics of cough sound signals. In this paper, we designed a cough-based respiratory disease classification system and proposed audio characteristic-dependent feature extraction and data augmentation methods. Firstly, according to the short durations and rapid transition of different cough stages, we proposed maximum overlapping mel-spectrogram to avoid missing inter-frame information caused by traditional framing methods. Secondly, we applied various data augmentation methods to mitigate the problem of limited labeled data. Based on the frequency energy distributions of different diseased cough audios, we proposed a parameter-independent self-energy-based augmentation method to enhance the differences between different frequency bands. Finally, in the model testing stage, we leveraged test-time augmentation to further improve the classification performance by fusing the test results of the original and multiple augmented audios. The proposed methods were validated on the Coswara dataset through stratified four-fold cross-validation. Compared to the baseline model using mel-spectrogram as input, the proposed methods achieved an average absolute performance improvement of 3.33% and 3.10% in macro Area Under the Receiver Operating Characteristic (macro AUC) and Unweighted Average Recall (UAR), respectively. The visualization results through Gradient-weighted Class Activation Mapping (Grad-CAM) showed the contributions of different features to model decisions.


Asunto(s)
Tos , Humanos , Tos/clasificación , Tos/fisiopatología , Procesamiento de Señales Asistido por Computador , Masculino , Femenino , Espectrografía del Sonido/métodos , Adulto , Persona de Mediana Edad
6.
J Biol Chem ; 300(9): 107598, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39059495

RESUMEN

In recent years, a surge in studies investigating N6-methyladenosine (m6A) modification in human diseases has occurred. However, the specific roles and mechanisms of m6A in kidney disease remain incompletely understood. This study revealed that m6A plays a positive role in regulating renal fibrosis (RF) by inducing epithelial-to-mesenchymal phenotypic transition (EMT) in renal tubular cells. Through comprehensive analyses, including m6A sequencing, RNA-seq, and functional studies, we confirmed the pivotal involvement of zinc finger E-box binding homeobox 2 (ZEB2) in m6A-mediated RF and EMT. Notably, the m6A-modified coding sequence of ZEB2 mRNA significantly enhances its translational elongation and mRNA stability by interacting with the YTHDF1/eEF-2 complex and IGF2BP3, respectively. Moreover, targeted demethylation of ZEB2 mRNA using the dm6ACRISPR system substantially decreases ZEB2 expression and disrupts the EMT process in renal tubular epithelial cells. In vivo and clinical data further support the positive influence of m6A/ZEB2 on RF progression. Our findings highlight the m6A-mediated regulation of RF through ZEB2, revealing a novel therapeutic target for RF treatment and enhancing our understanding of the impact of mRNA methylation on kidney disease.


Asunto(s)
Adenosina , Transición Epitelial-Mesenquimal , Fibrosis , Estabilidad del ARN , ARN Mensajero , Caja Homeótica 2 de Unión a E-Box con Dedos de Zinc , Caja Homeótica 2 de Unión a E-Box con Dedos de Zinc/metabolismo , Caja Homeótica 2 de Unión a E-Box con Dedos de Zinc/genética , Adenosina/análogos & derivados , Adenosina/metabolismo , Humanos , Animales , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratones , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Biosíntesis de Proteínas , Enfermedades Renales/metabolismo , Enfermedades Renales/genética , Enfermedades Renales/patología , Masculino , Riñón/metabolismo , Riñón/patología
7.
Int J Surg Pathol ; : 10668969241260811, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39053024

RESUMEN

Hepatoid adenocarcinoma of the ovary represents a rare and malignant extrahepatic tumor that shares morphological and immunophenotypic similarities with hepatocellular carcinoma. Due to the ambiguous histomorphology and aggressive behavior, the diagnosis and management of hepatoid adenocarcinoma of the ovary present unique challenges. Here, we present a 67-year-old woman with massive ascites and disseminated peritoneal implants at initial diagnosis. She was treated with six cycles of neoadjuvant therapy (albumin-bound paclitaxel + nedaplatin + bevacizumab) and a debulking surgery, followed by eight cycles of postoperative adjuvant therapy (albumin-bound paclitaxel + carboplatin + bevacizumab). Elaborate pathology workup found significant involvement of angiogenesis in the tumor and confirmed the diagnosis via immunohistochemistry. Further molecular characterization of the tumor by whole-exome sequencing (WES) revealed a novel heterozygous germline mutation (NM_000057.2, c.1290_1291delinsATCAGGCCTCCATAG, p.Y430fs1) in gene BLM, likely pathogenic, suggesting a potential candidate for Poly (ADP-ribose) polymerase (PARP) inhibitors. For the maintenance therapy, she received a combination of the PARP inhibitor niraparib and the antiangiogenic anlotinib. As of now, the patient has achieved a partial response, with no apparent evidence of disease progression observed nearly 30 months. Our study sheds light on the WES-based profiling in rare cancers to screen for any treatable targets with otherwise no standard therapeutic options. The promising results with the niraparib-anlotinib combination suggest its potential as a maintenance therapy option for hepatoid adenocarcinoma of the ovary, which warrants validation in future larger cohort.

8.
J Opt Soc Am A Opt Image Sci Vis ; 41(6): B48-B54, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38856403

RESUMEN

Structured beams have attracted increasing interest in free-space and fiber-based optical communications. Underwater wireless optical communication (UWOC) is becoming a prospective technique in marine exploration. We investigated UWOC performance using different representative structured beams. The transmission performances of the Gaussian, Bessel-Gaussian (BG), Ince-Gaussian (IG), and radially polarized Gaussian (RPG) beams were experimentally demonstrated and evaluated in underwater channels subjected to thermal gradient. The experimental results show that the BG, IG, and RPG perform better against the thermal gradient. Compared with the Gaussian beams, the beam wanders of BG, IG, and RPG beams under the thermal gradient have been reduced by 56.9%, 8.2%, and 59%, the scintillation indices have been decreased by 12.8%, 17.3%, and 28.9%, and the BER performance of the BG, IG, and RPG beams have been improved by ∼5.5, ∼3.7, and ∼5.2d B at the forward error correction threshold (FEC threshold). Based on the above results, the RPG beam is a more promising light source for UWOC. The experimental results provide a promising beam choice for UWOC.

9.
Emerg Microbes Infect ; 13(1): 2368217, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38865205

RESUMEN

Nipah virus (NiV), a highly pathogenic Henipavirus in humans, has been responsible for annual outbreaks in recent years. Experiments involving live NiV are highly restricted to biosafety level 4 (BSL-4) laboratories, which impedes NiV research. In this study, we developed transcription and replication-competent NiV-like particles (trVLP-NiV) lacking N, P, and L genes. This trVLP-NiV exhibited the ability to infect and continuously passage in cells ectopically expressing N, P, and L proteins while maintaining stable genetic characteristics. Moreover, the trVLP-NiV displayed a favourable safety profile in hamsters. Using the system, we found the NiV nucleoprotein residues interacting with viral RNA backbone affected viral replication in opposite patterns. This engineered system was sensitive to well-established antiviral drugs, innate host antiviral factors, and neutralizing antibodies. We then established a high-throughput screening platform utilizing the trVLP-NiV, leading to the identification of tunicamycin as a potential anti-NiV compound. Evidence showed that tunicamycin inhibited NiV replication by decreasing the infectivity of progeny virions. In conclusion, this trVLP-NiV system provided a convenient and versatile molecular tool for investigating NiV molecular biology and conducting antiviral drug screening under BSL-2 conditions. Its application will contribute to the development of medical countermeasures against NiV infections.


Asunto(s)
Infecciones por Henipavirus , Virus Nipah , Replicación Viral , Virus Nipah/fisiología , Virus Nipah/genética , Virus Nipah/efectos de los fármacos , Animales , Cricetinae , Humanos , Infecciones por Henipavirus/virología , Transcripción Genética , Virión/genética , Proteínas Virales/genética , Proteínas Virales/metabolismo , Antivirales/farmacología , Células Vero , Chlorocebus aethiops , Línea Celular , ARN Viral/genética
10.
Microbiol Spectr ; 12(7): e0001824, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38757960

RESUMEN

Monkeypox virus (MPXV) poses a global health threat. Droplet digital PCR (ddPCR) holds potential as an accurate diagnostic tool for clinical microbiology. However, there is limited literature on the applicability of ddPCR in clinical settings. In this study, the clinical features of patients with MPXV during the initial outbreak in China in June 2023 were reviewed, and an optimized ddPCR method with dilution and/or inhibitor removal was developed to enhance MPXV detection efficiency. Eighty-two MPXV samples were tested from nine different clinical specimen types, including feces, urine, pharyngeal swabs, anal swabs, saliva, herpes fluid, crust, and semen, and the viral load of each specimen was quantified. A comparative analysis was performed with qPCR to assess sensitivity and specificity and to investigate the characteristics of MPXV infection by analyzing viral loads in different clinical specimens. Consequently, common pharyngeal and gastrointestinal symptoms were observed in patients with MPXV. The optimized ddPCR method demonstrated relatively high sensitivity for MPXV quantification in the clinical materials, with a limit of detection of 0.1 copies/µL. This was particularly evident in low-concentration samples like whole blood, semen, and urine. The optimized ddPCR demonstrated greater detection accuracy compared with normal ddPCR and qPCR, with an area under the curve (AUC) of 0.939. Except for crust samples, viral loads in the specimens gradually decreased as the disease progressed. Virus levels in feces and anal swabs kept a high detection rate at each stage of post-symptom onset, and feces and anal swabs samples may be suitable for clinical diagnosis and continuous monitoring of MPXV. IMPORTANCE: The ddPCR technique proved to be a sensitive and valuable tool for accurately quantifying MPXV viral loads in various clinical specimen types. The findings provided valuable insights into the necessary pre-treatment protocols for MPXV diagnosis in ddPCR detection and the potentially suitable sample types for collection. Therefore, such results can aid in comprehending the potential characteristics of MPXV infection and the usage of ddPCR in clinical settings.


Asunto(s)
Monkeypox virus , Sensibilidad y Especificidad , Carga Viral , Humanos , Carga Viral/métodos , Monkeypox virus/aislamiento & purificación , Monkeypox virus/genética , China , Mpox/diagnóstico , Mpox/virología , Masculino , Heces/virología , Femenino , Reacción en Cadena de la Polimerasa/métodos , Brotes de Enfermedades , Adulto , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos
11.
Food Res Int ; 184: 114265, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38609243

RESUMEN

Radio frequency explosion puffing (RFEP) is a novel oil-free puffing technique used to produce crispy textured and nutritious puffed snacks. This study aimed to investigate the effects of freezing at different temperatures (-20 °C, -40 °C, -80 °C) for14 h and freezing times (1 and 2 times) on the cellular structure of purple sweet potato and the quality of RFEP chips. The analysis of cell microstructure, conductivity, and rheology revealed that higher freezing temperatures and more freezing times resulted in increased damage to the cellular structure, leading to greater cell membrane permeability and decreased cell wall stiffness. However, excessive damage to cellular structure caused tissue structure to collapse. Compared with the control group (4 °C), the RFEP sample pre-frozen once at -40 °C had a 47.13 % increase in puffing ratio and a 61.93 % increase in crispness, while hardness decreased by 23.44 % (p < 0.05). There was no significant change in anthocyanin retention or color difference. X-ray microtomography demonstrated that the RFEP sample pre-frozen once at -40 °C exhibited a more homogeneous morphology and uniform pore distribution, resulting in the highest overall acceptability. In conclusion, freezing pre-treatment before RFEP can significantly enhance the puffing quality, making this an effective method for preparing oil-free puffing products for fruits and vegetables.


Asunto(s)
Ipomoea batatas , Congelación , Explosiones , Pared Celular , Frío
12.
ACS Appl Mater Interfaces ; 16(11): 13496-13508, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38449094

RESUMEN

Atherosclerosis is a chronic inflammatory disease characterized by the formation of atherosclerotic plaques, while macrophages as key players in plaque progression and destabilization are promising targets for atherosclerotic plaque imaging. Contrast-enhanced magnetic resonance imaging (CE-MRI) has emerged as a powerful noninvasive imaging technique for the evaluation of atherosclerotic plaques within arterial walls. However, the visualization of macrophages within atherosclerotic plaques presents considerable challenges due to the intricate pathophysiology of the disease and the dynamic behavior of these cells. Biocompatible ferrite nanoparticles with diverse surface ligands possess the potential to exhibit distinct relaxivity and cellular affinity, enabling improved imaging capabilities for macrophages in atherosclerosis. In this work, we report macrophage-affinity nanoparticles for magnetic resonance imaging (MRI) of atherosclerosis via tailoring nanoparticle surface coating. The ultrasmall zinc ferrite nanoparticles (Zn0.4Fe2.6O4) as T1 contrast agents were synthesized and modified with dopamine, 3,4-dihydroxyhydrocinnamic acid, and phosphorylated polyethylene glycol to adjust their surface charges to be positively, negatively, and neutrally charged, respectively. In vitro MRI evaluation shows that the T1 relaxivity for different surface charged Zn0.4Fe2.6O4 nanoparticles was three higher than that of the clinically used Gd-DTPA. Furthermore, in vivo atherosclerotic plaque MR imaging indicates that positively charged Zn0.4Fe2.6O4 showed superior MRI efficacy on carotid atherosclerosis than the other two, which is ascribed to high affinity to macrophages of positively charged nanoparticles. This work provides improved diagnostic capability and a better understanding of the molecular imaging of atherosclerosis.


Asunto(s)
Aterosclerosis , Compuestos Férricos , Nanopartículas , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/diagnóstico por imagen , Placa Aterosclerótica/patología , Zinc , Aterosclerosis/patología , Medios de Contraste , Imagen por Resonancia Magnética/métodos , Macrófagos/patología
13.
Acta Pharmacol Sin ; 45(6): 1201-1213, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38491160

RESUMEN

The angiotensin II type 2 receptor (AT2R) is a well-established component of the renin-angiotensin system and is known to counteract classical activation of this system and protect against organ damage. Pharmacological activation of the AT2R has significant therapeutic benefits, including vasodilation, natriuresis, anti-inflammatory activity, and improved insulin sensitivity. However, the precise biological functions of the AT2R in maintaining homeostasis in liver tissue remain largely unexplored. In this study, we found that the AT2R facilitates liver repair and regeneration following acute injury by deactivating Hippo signaling and that interleukin-6 transcriptionally upregulates expression of the AT2R in hepatocytes through STAT3 acting as a transcription activator binding to promoter regions of the AT2R. Subsequently, elevated AT2R levels activate downstream signaling via heterotrimeric G protein Gα12/13-coupled signals to induce Yap activity, thereby contributing to repair and regeneration processes in the liver. Conversely, a deficiency in the AT2R attenuates regeneration of the liver while increasing susceptibility to acetaminophen-induced liver injury. Administration of an AT2R agonist significantly enhances the repair and regeneration capacity of injured liver tissue. Our findings suggest that the AT2R acts as an upstream regulator in the Hippo pathway and is a potential target in the treatment of liver damage.


Asunto(s)
Vía de Señalización Hippo , Interleucina-6 , Regeneración Hepática , Ratones Endogámicos C57BL , Proteínas Serina-Treonina Quinasas , Receptor de Angiotensina Tipo 2 , Transducción de Señal , Animales , Masculino , Ratones , Acetaminofén , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Hepatocitos/metabolismo , Hepatocitos/efectos de los fármacos , Interleucina-6/metabolismo , Hígado/metabolismo , Hígado/efectos de los fármacos , Regeneración Hepática/efectos de los fármacos , Regeneración Hepática/fisiología , Ratones Noqueados , Proteínas Serina-Treonina Quinasas/metabolismo , Receptor de Angiotensina Tipo 2/metabolismo , Transducción de Señal/efectos de los fármacos , Factor de Transcripción STAT3/metabolismo , Proteínas Señalizadoras YAP/metabolismo
14.
Perioper Med (Lond) ; 13(1): 7, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38355657

RESUMEN

BACKGROUND: This study was performed to analyze the clinical effect of different concentrations of ropivacaine in the labor analgesia of the dural puncture epidural (DPE) technique for obese puerperae. METHODS: One hundred and fifty first-term obese women who received vaginal delivery and required labor analgesia in our hospital were selected prospectively for this study, and divided into groups A, B, and C. The three groups of puerpera were given epidurals with different concentrations of ropivacaine (0.075%, 0.10%, and 0.125%) with sufentanil (0.5 µg/ml) for the labor analgesia regimen. The visual analog scale (VAS), Ramsay scale, and Bromage scale of puerperae before analgesia and at different time points after anesthesia, and analgesic onset time, analgesia time, first PCEA time, PCEA pressing time, ropivacaine consumption, labor time, maternal blood pressure and heart rate, maternal adverse reactions, blood gas analysis in the neonatal umbilical artery, and Apgar score were observed. RESULTS: The analgesia onset time, PCEA pressing time, and ropivacaine consumption in group C were lower and the analgesia time and the first PCEA time were longer than those in groups A and B. At T1-T3 and T5, VAS scores of group A were higher than those in groups B and C, Ramsay score of group A was lower than that of groups B and C at T2-T3, and Bromage score of group C at any time point was higher than other two groups. The time of the second stage of labor in groups B and C was longer than that in group A, which in group C was longer than that in group B. Compared with groups A and C, the blood pressure and heart rate of puerperae in group B were closer to normal values. Three different concentrations of ropivacaine had no significant effect on the umbilical artery blood gas analysis indices and Apgar scores at 1st minute and 5th minute in neonates. The incidence of maternal adverse reactions in group C was lower than those in groups A and B. CONCLUSION: 0.1% ropivacaine combined with 0.5 µg/ml sufentanil through DPE technique has good analgesic efficacy and few adverse effects in obese puerperae.

15.
Emerg Microbes Infect ; 13(1): 2300762, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38164794

RESUMEN

Ebola virus (EBOV) belongs to Filoviridae family possessing single-stranded negative-sense RNA genome, which is a serious threat to human health. Nowadays, no therapeutics have been proven to be successful in efficiently decreasing the mortality rate. RNA binding proteins (RBPs) are reported to participate in maintaining cell integrity and regulation of viral replication. However, little is known about whether and how RBPs participate in regulating the life cycle of EBOV. In our study, we found that RNA binding motif protein 4 (RBM4) inhibited the replication of EBOV in HEK293T and Huh-7 cells by suppressing viral mRNA production. Such inhibition resulted from the direct interaction between the RRM1 domain of RBM4 and the "CU" enrichment elements located in the PE1 and TSS of the 3'-leader region within the viral genome. Simultaneously, RBM4 could upregulate the expression of some cytokines involved in the host innate immune responses to synergistically exert its antiviral function. The findings therefore suggest that RBM4 might serve as a novel target of anti-EBOV strategy.


Asunto(s)
Ebolavirus , Fiebre Hemorrágica Ebola , Humanos , Ebolavirus/genética , ARN , Células HEK293 , Replicación Viral , Motivos de Unión al ARN , Genómica , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo
16.
Cell Signal ; 113: 110935, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37866666

RESUMEN

The renin-angiotensin system (RAS) has been recognized as a crucial contributor to the development of liver fibrosis, and AT2R, an essential component of RAS, is involved in the progression of liver fibrosis. However, the underlying mechanisms by which AT2R modulates liver fibrosis remain elusive. Here, we report that AT2R was induced to be highly expressed during the progression of liver fibrosis, and the elevated AT2R attenuates liver fibrosis by suppressing IRE1α-XBP1 pathway. In this study, we found that AT2R is not expressed in the no cirrhotic adult liver, but is induced expression during liver fibrosis in both cirrhotic patients and fibrotic mice models. Upregulated AT2R inhibits the activation and proliferation of hepatic stellate cells (HSCs). In addition, our study showed that during liver fibrosis, AT2R deletion increased the dimerization activation of IRE1α and promoted XBP1 splicing, and the spliced XBP1s could promote their transcription by binding to the AT2R promoter and repress the IRE1α-XBP1 axis, forming an AT2R-IRE1α-XBP1 negative feedback loop. Importantly, the combination treatment of an AT2R agonist and an endoplasmic reticulum stress (ER stress) alleviator significantly attenuated liver fibrosis in a mouse model of liver fibrosis. Therefore, we conclude that the AT2R-IRE1α signaling pathway can regulate the progression of liver fibrosis, and AT2R is a new potential therapeutic target for treating liver fibrosis.


Asunto(s)
Endorribonucleasas , Proteínas Serina-Treonina Quinasas , Humanos , Adulto , Ratones , Animales , Proteínas Serina-Treonina Quinasas/metabolismo , Endorribonucleasas/metabolismo , Angiotensina II , Transducción de Señal , Estrés del Retículo Endoplásmico , Cirrosis Hepática , Proteína 1 de Unión a la X-Box/genética , Proteína 1 de Unión a la X-Box/metabolismo
17.
Small ; : e2309918, 2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-38084467

RESUMEN

Anode materials with high-rate performances and good electrochemical stabilities are urgently required for the grid-scale application of lithium-ion batteries (LIBs). Theoretically, transition metal borides are desirable candidates because of their appropriate working potentials and good conductivities. However, the reported metal borides exhibit poor performances owing to their lack of favorable Li+ storage sites and poor structural stabilities during long-term charging/discharging. In this work, a ternary alkali metal boride, Li1.2 Ni2.5 B2 , which displays a high Li+ storage capacity and remarkable electrochemical stability and an excellent rate performance is studied. In contrast to conventional transition metal borides, the introduction of Li atoms facilitates the formation of 1D Ni/B-based honeycomb channels during synthesis. This Ni/B framework successfully sustains the strain during Li+ intercalation and deintercalation, and thus, the optimized Li1.2 Ni2.5 B2 anode exhibits an excellent cycle stability over 500 charge/discharge cycles. This electrode also exhibits superior reversible capacities of 350, 183, and 80 mA h g-1 at 0.1, 1, and 5 A g-1 , respectively, indicating the considerable potential of the 1D Ni/B framework as a commercially available fast-charging LIB anode.

18.
Sci Rep ; 13(1): 17860, 2023 10 19.
Artículo en Inglés | MEDLINE | ID: mdl-37857681

RESUMEN

Linear biometric measurements on magnetic resonance images are important for the assessment of fetal brain development, which is expert knowledge dependent and laborious. This study aims to construct a segmentation-based method for automatic two-dimensional biometric measurements of fetal brain on magnetic resonance images that provides a fast and accurate measurement of fetal brain. A total of 268 volumes (5360 images) magnetic resonance images of normal fetuses were included. The automatic method involves two steps. First, the fetal brain was segmented into four parts with a deep segmentation network: cerebrum, cerebellum, and left and right lateral ventricles. Second, the measurement plane was determined, and the corresponding biometric parameters were calculated according to clinical guidelines, including cerebral biparietal diameter (CBPD), transverse cerebellar diameter (TCD), left and right atrial diameter (LAD/RAD). Pearson correlation coefficient and Bland-Altman plots were used to assess the correlation and agreement between computer-predicted values and manual measurements. Mean differences were used to evaluate the errors quantitatively. Analysis of fetal cerebral growth based on the automatic measurements was also displayed. The experiment results show that correlation coefficients for CBPD, TCD, LAD and RAD were as follows: 0.977, 0.990, 0.817, 0.719, mean differences were - 2.405 mm, - 0.008 mm, - 0.33 mm, - 0.213 mm, respectively. The correlation between the errors and gestational age was not statistically significant (p values were 0.2595, 0.0510, 0.1995, and 0.0609, respectively). The proposed automatic method for linear measurements on fetal brain MRI achieves excellent performance, which is expected to be applied in clinical practice and be helpful for prenatal diagnosis and clinical work efficiency improvement.


Asunto(s)
Biometría , Ultrasonografía Prenatal , Femenino , Embarazo , Humanos , Ultrasonografía Prenatal/métodos , Biometría/métodos , Feto/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Aprendizaje Automático
19.
Genes (Basel) ; 14(8)2023 07 30.
Artículo en Inglés | MEDLINE | ID: mdl-37628612

RESUMEN

The proper supplementation of boron, an essential trace element, can enhance animal immune function. We utilized the method of TMT peptide labeling in conjunction with LC-MS/MS quantitative proteomics for the purpose of examining the effects of boric acid on a rat model and analyzing proteins from the duodenum. In total, 5594 proteins were obtained from the 0, 10, and 320 mg/L boron treatment groups. Two hundred eighty-four proteins that exhibit differential expression were detected. Among the comparison, groups of 0 vs. 10 mg/L, 0 vs. 320 mg/L, and 10 vs. 320 mg/L of boron, 110, 32, and 179 proteins, respectively, demonstrated differential expression. The results revealed that these differential expression proteins (DEPs) mainly clustered into two profiles. GO annotations suggested that most of the DEPs played a role in the immune system process, in which 2'-5'-oligoadenylate synthetase-like, myxovirus resistance 1, myxovirus resistance 2, dynein cytoplasmic 1 intermediate chain 1, and coiled-coil domain containing 88B showed differential expression. The DEPs had demonstrated an augmentation in the signaling pathways, which primarily include phagosome, antigen processing, and presentation, as well as cell adhesion molecules (CAMs). Our study found that immune responses in the duodenum were enhanced by lower doses of boron and that this effect is likely mediated by changes in protein expression patterns in related signaling pathways. It offers an in-depth understanding of the underlying molecular mechanisms that lead to immune modulation in rats subjected to dietary boron treatment.


Asunto(s)
Boro , Proteómica , Animales , Ratas , Boro/farmacología , Cromatografía Liquida , Espectrometría de Masas en Tándem , Duodeno , Suplementos Dietéticos
20.
Small ; 19(52): e2304373, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37649179

RESUMEN

Lithium metal anodes face several challenges in practical applications, such as dendrite growth, poor cycle efficiency, and volume variation. 3D hosts with lithiophilic surfaces have emerged as a promising design strategy for anodes. In this study, inspiration from the intrinsic isotropy, chemical heterogeneity, and wide tunability of metallic glass (MG) is drew to develop a 3D mesoporous host with a lithiophilic surface. The CuZrAg MG is prepared using the scalable melt-spinning technique and subsequently treated with a simple one-step chemical dealloying method. This resultes in the creation of a host with a homogeneously distributed abundance of lithium affinity sites on the surface. The excellent lithiophilic property and capability for uniform lithium deposition of the 3D CuZrAg electrode have been confirmed through theoretical calculations. Therefore, the 3D CuZrAg electrode displays excellent cyclic stability for over 400 cycles with 96% coulomb efficiency, and ultra-low overpotentials of 5 mV for over 2000 h at 1.0 mA cm-2 and 1.0 mAh cm-2 . Additionally, the full cells partied with either LiFePO4 or LiNi0.8 Co0.1 Mn0.1 O2 cathode deliver exceptional long-term cyclability and rate capability. This work demonstrates the great potential of metallic glass in lithium metal anode application.

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