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1.
J Am Chem Soc ; 146(30): 20668-20677, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39031766

RESUMEN

Lower olefins are widely used in the chemical industry as basic carbon-based feedstocks. Here, we report the catalytic system featuring isolated single-atom sites of iridium (Ir1) that can function within the entire temperature range of 300-600 °C and transform alkanes with conversions close to thermodynamics-dictated levels. The high turnover frequency values of the Ir1 system are comparable to those of homogeneous catalytic reactions. Experimental data and theoretical calculations both indicate that Ir1 is the primary catalytic site, while the coordinating C and N atoms help to enhance the activity and stability, respectively; all three kinds of elements cooperatively contribute to the high performance of this novel active site. We have further immobilized this catalyst on particulate Al2O3, and we found that the resulting composite system under mimicked industrial conditions could still give high catalytic performances; in addition, we have also developed and established a new scheme of periodical in situ regeneration specifically for this composite particulate catalyst.

2.
Funct Integr Genomics ; 24(2): 63, 2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38517555

RESUMEN

The TRIM family is associated with the membrane, and its involvement in the progression, growth, and development of various cancer types has been researched extensively. However, the role played by the TRIM5 gene within this family has yet to be explored to a great extent in terms of hepatocellular carcinoma (HCC). The data of patients relating to mRNA expression and the survival rate of individuals diagnosed with HCC were extracted from The Cancer Genome Atlas (TCGA) database. UALCAN was employed to examine the potential link between TRIM5 expression and clinicopathological characteristics. In addition, enrichment analysis of differentially expressed genes (DEGs) was conducted as a means of deciphering the function and mechanism of TRIM5 in HCC. The data in the TCGA and TIMER2.0 databases was utilized to explore the correlation between TRIM5 and immune infiltration in HCC. WGCNA was performed as a means of assessing TRIM5-related co-expressed genes. The "OncoPredict" R package was also used for investigating the association between TRIM5 and drug sensitivity. Finally, qRT-PCR, Western blotting (WB) and immunohistochemistry (IHC) were employed for exploring the differential expression of TRIM5 and its clinical relevance in HCC. According to the results that were obtained from the vitro experiments, mRNA and protein levels of TRIM5 demonstrated a significant upregulation in HCC tissues. It is notable that TRIM5 expression levels were found to have a strong association with the infiltration of diverse immune cells and displayed a positive correlation with several immune checkpoint inhibitors. The TRIM5 expression also displayed promising clinical prognostic value for HCC patients.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Expresión Génica , ARN Mensajero , Biomarcadores , Proteínas de Motivos Tripartitos/genética , Factores de Restricción Antivirales , Ubiquitina-Proteína Ligasas
3.
Small ; : e2406860, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39233543

RESUMEN

Myeloid-derived suppressor cells (MDSCs) are reported to be responsible for the negative prognosis of colorectal cancer (CRC) patients due to the mediated immunosuppressive tumor microenvironment (TME). The selective and chronic circumvention of tumor-infiltrated MDSCs has potential clinical significance for CRC treatment, which unluckily remains a technical challenge. Because tumor hypoxia makes a significant contribution to the recruitment of MDSCs in tumor sites, a dual oxygen-supplied immunosuppression-inhibiting nanomedicine (DOIN) is demonstrated for overcoming tumor hypoxia, which achieves selective and long-term inhibition of intratumoral recruitment of MDSCs. The DOIN is constructed by the encasement of perfluorooctyl bromide (PFOB) and 4-methylumbelliferone (4-MU) into a TME-responsive amphiphilic polymer. This nanoplatform directly carries oxygen to the tumor region and simultaneously loosens the condensed tumor extracellular matrix for the normalization of tumor vasculature, which selectively remodels the TME toward one adverse to the intratumoral recruitment of MDSCs. Importantly, this nanoplatform offers a long-acting alleviation of the hypoxic TME, chronically avoiding the comeback of tumor-infiltrated MDSCs. Consequently, the immunosuppressive TME is relieved, and T cells are successfully proliferated and activated into cytotoxic T lymphocytes, which boosts a systemic immune response and contributes to lasting inhibition of tumor growth with a prolonged survival span of xenograft.

4.
Small ; 20(7): e2306227, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37806748

RESUMEN

γ-valerolactone (GVL) is a key value-added chemical catalytically produced from levulinic acid (LA), an important biomass derivative platform chemical. Here an ultra-efficient 3D Ru catalyst generated by in situ reduction of RuZnOx nanoboxes is reported; the catalyst features a well-defined structure of highly dispersed in situ oxide-derived Ru (IOD-Ru) clusters (≈1 nm in size) spatially confined within the 3D nanocages with rich mesopores, which guarantees a maximized atom utilization with a high exposure of Ru active sites as well as a 3D accessibility for substrate molecules. The IOD-Ru exhibits ultrahigh performance for the hydrogenation of LA into GVL with a record-breaking turnover frequency (TOF) up to 59400 h-1 , 14 times higher than that of the ex situ reduction of RuZnOx nanoboxes catalyst. Structural characterizations and theoretical calculations collectively indicate that the defect-rich and coordination-unsaturated IOD-Ru sites can boost the activation of the carbonyl group in LA with a significantly lowered energy barrier of hydrogenation.

5.
Microb Pathog ; 187: 106515, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38160987

RESUMEN

In this study, a low molecular weight poly-d-mannose (LMWM) was separated from a mixed polysaccharide synthesized previously. Monosaccharide composition, Fourier-Transform infrared spectroscopy (FT-IR), periodate oxidation and smith degradation were determined. After safety evaluation, the inhibition of LMWM on the different biofilm formation stages of Salmonella enterica serovar Typhimurium (S. Typhimurium) was tested in vitro. Furthermore, the effect of LMWM on the adhesion of S. Typhimurium to Caco-2 cells and cell surface hydrophobicity (CSH) were observed. Results indicated that LMWM was a homopolysaccharide without cytotoxicity and hemolysis, containing both α-mannose and ß-mannose. It showed obvious anti-biofilm activity on S. Typhimurium and mainly activated on the initial adhesion and formation stage, even better than the commercial S. cerevisiae mannan (CM). LMWM inhibited the adhesion of S. Typhimurium on Caco-2 cells with the inhibition rate of 61.04 % at 2 mg/ml. Meanwhile, LMWM decreased the hydrophobicity of S. Typhimurium cell surface. In conclusion, the inhibitory effect on S. Typhimurium biofilm was not caused by bacteriostatic or bactericidal activity of LMWM. The specific anti-adhesion and the decrease of bacterial CSH by LMWM may closely relate to anti-biofilm mechanism. This study provides some supports for the application of LMWM as antibiotics alternative on S. Typhimurium in the future.


Asunto(s)
Manosa , Salmonella typhimurium , Humanos , Manosa/metabolismo , Manosa/farmacología , Células CACO-2 , Peso Molecular , Saccharomyces cerevisiae , Espectroscopía Infrarroja por Transformada de Fourier , Biopelículas
6.
Eur Radiol ; 34(1): 509-524, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37507611

RESUMEN

OBJECTIVES: To investigate the efficiency of a combination of preoperative contrast-enhanced computed tomography (CECT) and carbohydrate antigen 19-9 (CA19-9) in predicting disease-free survival (DFS) after R0 resection of pancreatic ductal adenocarcinoma (PDAC). METHODS: A total of 138 PDAC patients who underwent curative R0 resection were retrospectively enrolled and allocated chronologically to training (n = 91, January 2014-July 2019) and validation cohorts (n = 47, August 2019-December 2020). Using univariable and multivariable Cox regression analyses, we constructed a preoperative clinicoradiographic model based on the combination of CECT features and serum CA19-9 concentrations, and validated it in the validation cohort. The prognostic performance was evaluated and compared with that of postoperative clinicopathological and tumor-node-metastasis (TNM) models. Kaplan-Meier analysis was conducted to verify the preoperative prognostic stratification performance of the proposed model. RESULTS: The preoperative clinicoradiographic model included five independent prognostic factors (tumor diameter on CECT > 4 cm, extrapancreatic organ infiltration, CECT-reported lymph node metastasis, peripheral enhancement, and preoperative CA19-9 levels > 180 U/mL). It better predicted DFS than did the postoperative clinicopathological (C-index, 0.802 vs. 0.787; p < 0.05) and TNM (C-index, 0.802 vs. 0.711; p < 0.001) models in the validation cohort. Low-risk patients had significantly better DFS than patients at the high-risk, defined by the model preoperatively (p < 0.001, training cohort; p < 0.01, validation cohort). CONCLUSIONS: The clinicoradiographic model, integrating preoperative CECT features and serum CA19-9 levels, helped preoperatively predict postsurgical DFS for PDAC and could facilitate clinical decision-making. CLINICAL RELEVANCE STATEMENT: We constructed a simple model integrating clinical and radiological features for the prediction of disease-free survival after curative R0 resection in patients with pancreatic ductal adenocarcinoma; this novel model may facilitate preoperative identification of patients at high risk of recurrence and metastasis that may benefit from neoadjuvant treatments. KEY POINTS: • Existing clinicopathological predictors for prognosis in pancreatic ductal adenocarcinoma (PDAC) patients who underwent R0 resection can only be ascertained postoperatively and do not allow preoperative prediction. • We constructed a clinicoradiographic model, using preoperative contrast-enhanced computed tomography (CECT) features and preoperative carbohydrate antigen 19-9 (CA19-9) levels, and presented it as a nomogram. • The presented model can predict disease-free survival (DFS) in patients with PDAC better than can postoperative clinicopathological or tumor-node-metastasis (TNM) models.


Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Antígeno CA-19-9 , Supervivencia sin Enfermedad , Estudios Retrospectivos , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/cirugía , Carcinoma Ductal Pancreático/diagnóstico por imagen , Carcinoma Ductal Pancreático/cirugía , Pronóstico , Tomografía Computarizada por Rayos X/métodos , Carbohidratos
7.
Clin Exp Rheumatol ; 42(2): 237-245, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38153165

RESUMEN

OBJECTIVES: Anti-MDA5+ dermatomyositis was associated with poor prognosis due to the high incidence of rapid progressive interstitial lung disease, pulmonary infection. The aim of this study is to investigate the abundance and clinical relevance of exhaustion markers on peripheral CD8 T cells from patients with idiopathic inflammatory myopathy (IIM). METHODS: Twenty-nine healthy controls (HCs) and 71 patients with IIM were enrolled, including 42 with anti-MDA5+ and 18 with anti-MDA5- dermatomyositis (DM) and 11 with anti-synthetase syndrome (ASS). Flow cytometry was applied to detect PD-1, TIM-3 and LAG-3 in CD8 T cells. The clinical associations of the CD8 T cell exhaustion phenotype in patients with anti-MDA5+ DM were analysed. RESULTS: CD8 T cells from patients with anti-MDA5+ DM showed significantly increased LAG-3, TIM-3 and PD-1 compared to those from patients with anti-MDA5- IIM (18 with anti-MDA5- DM and 11 with ASS) or HCs (adjusted p all < 0.05). CD8 T cells with distinct exhaustion levels were all significantly increased in anti-MDA5+ DM patients compared with HCs (p all < 0.05). Patients with high level of PD-1+ TIM-3+LAG-3+ CD8+ T cells had a significant higher incidence of pulmonary fungal infections but lower counts of CD4+ and CD8+ T cells. ROC analysis revealed that the frequency of PD-1+TIM-3+LAG-3+CD8+ T cell significantly predicted pulmonary fungal infections (area under the curve: 0.828). CONCLUSIONS: CD8 T cells from patients with anti-MDA5+ DM show significant exhausted phenotype, and increased exhausted CD8 T cells were associated with high risk of pulmonary fungal infection.


Asunto(s)
Dermatomiositis , Humanos , Dermatomiositis/complicaciones , Receptor 2 Celular del Virus de la Hepatitis A , Helicasa Inducida por Interferón IFIH1 , Receptor de Muerte Celular Programada 1 , Autoanticuerpos , Linfocitos T CD8-positivos , Linfocitos T , Estudios Retrospectivos , Pronóstico
8.
Nanotechnology ; 35(48)2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39208809

RESUMEN

The distinctive multi-ring structure and remarkable electrical characteristics of biphenylene render it a material of considerable interest, notably for its prospective utilization as an anode material in lithium-ion batteries. However, understanding the mechanical traits of biphenylene is essential for its application, particularly due to the volumetric fluctuations resulting from lithium ion insertion and extraction during charging and discharging cycles. In this regard, this study investigates the performance of pristine biphenylene and materials embedded with various types of hole defects under uniaxial tension utilizing molecular dynamics simulations. Specifically, from the stress‒strain curves, we obtained key mechanical properties, including toughness, strength, Young's modulus and fracture strain. It was observed that various near-circular hole (including circular, square, hexagonal, and octagonal) defects result in remarkably similar properties. A more quantitative scaling analysis revealed that, in comparison with the exact shape of the defect, the area of the defect is more critical for determining the mechanical properties of biphenylene. Our finding might be beneficial to the defect engineering of two-dimensional materials.

9.
Nanotechnology ; 35(21)2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38382120

RESUMEN

Thermal effect remains a thorny issue for femtosecond-laser surface engineering and nanostructuring on metallic targets with high pulse energies or high repetition rates, which needs to be paid adequate attentions. Herein, we have experimentally investigated the heat diffusion and accumulations during single-shot and multi-shot femtosecond laser ablation on metallic surfaces. We have for the first time observed a novel phenomenon that the thermal effect was intensified abruptly when the laser-pulse number goes over a threshold (approximately between 10 and 20 for aluminum alloy with laser fluence of 6 J cm-2), accompanied with a dramatic reduction of ablated depth and complicated plasma dynamics. Based on both optical and thermodynamic analysis, we introduced a defocusing-dominated plasma-assistant model for this abnormal thermal effect. This work explored the critical experimental parameters for femtosecond-laser surface modification and processing in micro-scale engineering applications.

10.
Mol Biol Rep ; 51(1): 762, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38874690

RESUMEN

BACKGROUND: Hepatocellular carcinoma (HCC) is experiencing a concerning rise in both incidence and mortality rates. Current therapeutic strategies are limited in their effectiveness, largely due to the complex causes of the disease and significant levels of drug resistance. Given the latest developments in human umbilical cord mesenchymal stem cells (hUC-MSCs) research, there is a debate over the continued use of stem cell transplantation for treating tumors. Consequently, this study seeks to explore the role of hUC-MSCs in the management of HCC. METHODS AND RESULTS: HUC-MSCs increased the number (10.75 ± 1.50) in the DEN/TCPOBOP-induced mice hepatoma model, compared with DMSO group (7.25 ± 1.71). Moreover, the liver index in hUC-MSCs group (0.21 ± 0.06) was greater than that in DMSO group (0.09 ± 0.01). Immunohistochemical (IHC) analysis revealed that while hUC-MSCs did not alter Foxp3 expression, they significantly stimulated Ki67 expression, indicative of increased tumor cellular proliferation. Additionally, immunofluorescence (IF) studies showed that hUC-MSCs increased CD8+ T cell counts without affecting macrophage numbers. Notably, granzyme B expression remained nearly undetectable. We observed that serum IL-18 levels were higher in the hUC-MSCs group (109.66 ± 0.38 pg/ml) compared to the DMSO group (91.14 ± 4.37 pg/ml). Conversely, IL-1ß levels decreased in the hUC-MSCs group (63.00 ± 0.53 pg/ml) relative to the DMSO group (97.38 ± 9.08 pg/ml). CONCLUSIONS: According to this study, hUC-MSCs promoted the growth of liver tumors. Therefore, we proposed that hUC-MSCs are not suitable for treating HCC, as they exhibit clinically prohibited abnormalities.


Asunto(s)
Carcinoma Hepatocelular , Proliferación Celular , Interleucina-18 , Neoplasias Hepáticas , Células Madre Mesenquimatosas , Cordón Umbilical , Células Madre Mesenquimatosas/metabolismo , Humanos , Animales , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/metabolismo , Cordón Umbilical/citología , Interleucina-18/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/terapia , Ratones , Trasplante de Células Madre Mesenquimatosas/métodos , Masculino , Línea Celular Tumoral , Linfocitos T CD8-positivos/metabolismo , Linfocitos T CD8-positivos/inmunología
11.
Exp Cell Res ; 424(1): 113486, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36693491

RESUMEN

Anti-PD-1 immunotherapy is a promising treatment for hepatocellular carcinoma (HCC), but some patients with HCC do not experience clinical benefits. Autophagy promotes tumor progression and participates in drug resistance. Previous studies have revealed that suppressing the expression level of Yes-associated protein 1 (YAP1) improves anti-PD-1 therapy efficacy. Therefore, the relationship between YAP1 expression and autophagy activity during anti-PD-1 treatment was investigated in this study. A positive correlation was found between the expression level of YAP1 and LC3B by analyzing The Cancer Genome Atlas (TCGA), UALCAN databases, and HCC tissue microarray. Meanwhile, YAP1 expression and autophagy constituted positive feedback, in which YAP1 inhibition decreased the autophagy activity in liver tumor cells by hepatocyte-specific Yap1 knockout mice. Further, anti-PD-1 treatment increased autophagy and YAP1 expression levels in the cancer tissues from DEN/TCPOBOP-induced liver cancer mice. Finally, Yap1 knockout suppressed autophagy and improved anti-PD-1 therapy efficacy in hepatocyte-specific Yap1 knockout mice with liver tumors. These results suggested that YAP1 suppression was sensitized to anti-PD-1 treatment and inhibited autophagy activity in liver tumor cells. YAP1 is a promising target for improving the efficacy of anti-PD-1 immunotherapy in HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animales , Ratones , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Autofagia , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Inmunoterapia , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Ratones Noqueados , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Humanos
12.
Mod Rheumatol ; 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39190552

RESUMEN

OBJECTIVES: We aimed to assess the sleep quality of patients with primary Sjögren's syndrome (pSS) and the associated factors. Moreover, Preliminary exploration of the clinical significance of serum brain-derived neurotrophic factor (BDNF) in pSS patients with sleep disorders. METHODS: A self-report survey was administered to 111 pSS patients and 40 healthy individuals using the Pittsburgh Sleep Quality Index (PSQI) for sleep quality. General clinical information,the sleep quality and mental conditions were collected using on-site questionnaires and various scales. 40 healthy controls from the health examination center of the same hospital, who were age and sex matched. Detection of serum BDNF levels by ELISA method . Independent samples t tests, Chi-square analysis, logistic regression were used to analyze these data. RESULTS: Patients with pSS had higher scores on the PSQI than the healthy individuals. Abnormal sweating, high PHQ-9 and ESSPRI scores were independent risk factors for sleep disorders. pSS patients had lower serum BDNF than the healthy individuals, The area under the curve (AUC) of predicting sleep disorder in pSS patients using detection of serum BDNF level was 0.8470, and the sensitivity and specificity were 0.951 and 0.727, which were superior to PHQ-9 and GAD-7. CONCLUSION: Compared with the healthy individuals, pSS patients had a higher prevalence of sleep disorders and lower serum BNDF. Serum BDNF level demonstrated greater predictive advantage for sleep disorder in pSS patients.

13.
Zhongguo Zhong Yao Za Zhi ; 49(5): 1295-1309, 2024 Mar.
Artículo en Zh | MEDLINE | ID: mdl-38621977

RESUMEN

The aim of this study was to explore the mechanism of icaritin-induced ferroptosis in hepatoma HepG2 cells. By bioinformatics screening, the target of icariin's intervention in liver cancer ferroptosis was selected, the protein-protein interaction(PPI) network was constructed, the related pathways were focused, the binding ability of icariin and target protein was evaluated by molecular docking, and the impact on patients' survival prognosis was predicted and the clinical prediction model was built. CCK-8, EdU, and clonal formation assays were used to detect cell viability and cell proliferation; colorimetric method and BODIPY 581/591 C1 fluorescent probe were used to detect the levels of Fe~(2+), MDA and GSH in cells, and the ability of icariin to induce HCC cell ferroptosis was evaluated; RT-qPCR and Western blot detection were used to verify the mRNA and protein levels of GPX4, xCT, PPARG, and FABP4 to determine the expression changes of these ferroptosis-related genes in response to icariin. Six intervention targets(AR, AURKA, PPARG, AKR1C3, ALB, NQO1) identified through bioinformatic analysis were used to establish a risk scoring system that aids in estimating the survival prognosis of HCC patients. In conjunction with patient age and TNM staging, a comprehensive Nomogram clinical prediction model was developed to forecast the 1-, 3-, and 5-year survival of HCC patients. Experimental results revealed that icariin effectively inhibited the activity and proliferation of HCC cells HepG2, significantly modulating levels of Fe~(2+), MDA, and lipid peroxidation ROS while reducing GSH levels, hence revealing its potential to induce ferroptosis in HCC cells. Icariin was found to diminish the expression of GPX4 and xCT(P<0.01), inducing ferroptosis in HCC cells, potentially in relation to inhibition of PPARG and FABP4(P<0.01). In summary, icariin induces ferroptosis in HCC cells via the PPARG/FABP4/GPX4 pathway, providing an experimental foundation for utilizing the traditional Chinese medicine icariin in the prevention or treatment of HCC.


Asunto(s)
Carcinoma Hepatocelular , Ferroptosis , Flavonoides , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , PPAR gamma , Células Hep G2 , Modelos Estadísticos , Simulación del Acoplamiento Molecular , Pronóstico , Proteínas de Unión a Ácidos Grasos
14.
Zhongguo Zhong Yao Za Zhi ; 49(11): 3040-3049, 2024 Jun.
Artículo en Zh | MEDLINE | ID: mdl-39041164

RESUMEN

This study aims to explore the effect of Lycii Fructus and Salviae Miltiorrhizae Radix et Rhizoma(LFSMR), a drug pair possesses the function of nourishing Yin, promoting blood circulation, and brightening the eyes, in treating retinitis pigmentosa(RP)by inhibiting the gliosis of Müller cells(MCs) and inducing their reprogramming and differentiation into various types of retinal nerve cells. Twelve C57 mice were used as the normal control group, and 48 transgenic RP(rd10) mice were randomly divided into the model group, positive control group, and low and high dose LFSMR groups, with 12 mice in each group. HE staining was used to detect pathological changes in the retina, and an electroretinogram was used to detect retinal function. Retinal optical coherence tomography was used to detect retinal thickness and perform fundus photography, and laser speckle perfusion imaging was used to detect local retinal blood flow. Digital PCR was used to detect gene expression related to retinal nerve cells, and immunofluorescence was used to detect protein expression related to retinal nerve cells. LFSMR could significantly improve the pathological changes, increase the amplitude of a and b waves, increase the retinal thickness, restore retinal damage, and increase retinal blood flow in mice with RP lesions. LFSMR could also significantly inhibit the m RNA expression of the glial fibrillary acidic protein( GFAP) during the pathogenesis of RP and upregulate m RNA expression of sex determining region Y box protein 2(SOX2), paired box protein 6(Pax6),rhodopsin, protein kinase C-α(PKCα), syntaxin, and thymic cell antigen 1. 1(Thy1. 1). LFSMR could significantly inhibit GFAP protein expression and enhance protein expression of SOX2, Pax6, rhodopsin, PKCα, syntaxin, and Thy1. 1. It could also reverse the pathological changes in the retina of rd10 mice, improve retinal function and fundus performance, increase retinal thickness, enhance local retinal blood flow, and exert therapeutic effects on RP. The mechanism of action of LFSMR may be related to inhibiting the gliosis of MCs and promoting their reprogramming and differentiation into various types of retinal nerve cells.


Asunto(s)
Medicamentos Herbarios Chinos , Células Ependimogliales , Lycium , Ratones Endogámicos C57BL , Retinitis Pigmentosa , Salvia miltiorrhiza , Animales , Ratones , Células Ependimogliales/efectos de los fármacos , Células Ependimogliales/metabolismo , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/administración & dosificación , Lycium/química , Retinitis Pigmentosa/tratamiento farmacológico , Retinitis Pigmentosa/genética , Retinitis Pigmentosa/metabolismo , Retinitis Pigmentosa/fisiopatología , Salvia miltiorrhiza/química , Masculino , Retina/efectos de los fármacos , Rizoma/química , Humanos
15.
Angew Chem Int Ed Engl ; : e202410514, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38966937

RESUMEN

Organic scintillators are praised for their abundant element reserves, facile preparation procedures, and rich structures. However, the weak X-ray attenuation ability and low exciton utilization efficiency result in unsatisfactory scintillation performance. Herein, a new family of highly efficient organic phosphonium halide salts with thermally activated delayed fluorescence (TADF) are designed by innovatively adopting quaternary phosphonium as the electron acceptor, while dimethylamine group and halide anions (I-) serve as the electron donor. The prepared butyl(2-[2-(dimethylamino)phenyl]phenyl)diphenylphosphonium iodide (C4-I) exhibits bright blue emission and an ultra-high photoluminescence quantum yield (PLQY) of 100 %. Efficient charge transfer is realized through the unique n-π and anion-π stacking in solid-state C4-I. Photophysical studies of C4-I suggest that the incorporation of I accounts for high intersystem crossing rate (kISC) and reverse intersystem crossing rate (kRISC), suppressing the intrinsic prompt fluorescence and enabling near-pure TADF emission at room temperature. Benefitting from the large Stokes shift, high PLQY, efficient exciton utilization, and remarkable X-ray attenuation ability endowed by I, C4-I delivers an outstanding light yield of 80721 photons/MeV and a low limit of detection (LoD) of 22.79 nGy ⋅ s-1. This work would provide a rational design concept and open up an appealing road for developing efficient organic scintillators with tunable emission, strong X-ray attenuation ability, and excellent scintillator performance.

16.
J Am Chem Soc ; 145(12): 6658-6670, 2023 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-36802612

RESUMEN

Developing efficient and simple catalysts to reveal the key scientific issues in the epoxidation of ethylene has been a long-standing goal for chemists, whereas a heterogenized molecular-like catalyst is desirable which combines the best aspects of homogeneous and heterogeneous catalysts. Single-atom catalysts can effectively mimic molecular catalysts on account of their well-defined atomic structures and coordination environments. Herein, we report a strategy for selective epoxidation of ethylene, which exploits a heterogeneous catalyst comprising iridium single atoms to interact with the reactant molecules that act analogously to ligands, resulting in molecular-like catalysis. This catalytic protocol features a near-unity selectivity (99%) to produce value-added ethylene oxide. We investigated the origin of the improvement of selectivity for ethylene oxide for this iridium single-atom catalyst and attributed the improvement to the π-coordination between the iridium metal center with a higher oxidation state and ethylene or molecular oxygen. The molecular oxygen adsorbed on the iridium single-atom site not only helps to strengthen the adsorption of ethylene molecule by iridium but also alters its electronic structure, allowing iridium to donate electrons into the double bond π* orbitals of ethylene. This catalytic strategy facilitates the formation of five-membered oxametallacycle intermediates, leading to the exceptionally high selectivity for ethylene oxide. Our model of single-atom catalysts featuring remarkable molecular-like catalysis can be utilized as an effective strategy for inhibiting the overoxidation of the desired product. Implementing the concepts of homogeneous catalysis into heterogeneous catalysis would provide new perspectives for the design of new advanced catalysts.

17.
Eur J Nucl Med Mol Imaging ; 50(3): 881-891, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36301324

RESUMEN

PURPOSE: To compare PET/CT, MRI and ultrasonography in detecting recurrence of nasopharyngeal carcinoma and identify their benefit in staging, contouring and overall survival (OS). METHODS: Cohort A included 1453 patients with or without histopathology-confirmed local recurrence, while cohort B consisted of 316 patients with 606 histopathology-confirmed lymph nodes to compare the sensitivities and specificities of PET/CT, MRI and ultrasonography using McNemar test. Cohorts C and D consisted of 273 patients from cohort A and 267 patients from cohort B, respectively, to compare the distribution of PET/CT-based and MRI-based rT-stage and rN-stage and the accuracy of rN-stage using McNemar test. Cohort E included 30 random patients from cohort A to evaluate the changes in contouring with or without PET/CT by related-samples T test or Wilcoxon rank test. The OS of 61 rT3-4N0M0 patients staged by PET/CT plus MRI (cohort F) and 67 MRI-staged rT3-4N0M0 patients (cohort G) who underwent similar salvage treatment were compared by log-rank test and Cox regression. RESULTS: PET/CT had similar specificity to MRI but higher sensitivity (93.9% vs. 79.3%, P < 0.001) in detecting local recurrence. PET/CT, MRI and ultrasonography had comparable specificities, but PET/CT had greater sensitivity than MRI (90.9% vs. 67.6%, P < 0.001) and similar sensitivity to ultrasonography in diagnosing lymph nodes. According to PET/CT, more patients were staged rT3-4 (82.8% vs. 68.1%, P < 0.001) or rN + (89.9% vs. 69.3%, P < 0.001), and the rN-stage was more accurate (90.6% vs. 73.8%, P < 0.001). Accordingly, the contours of local recurrence were more precise (median Dice similarity coefficient 0.41 vs. 0.62, P < 0.001) when aided by PET/CT plus MRI. Patients staged by PET/CT plus MRI had a higher 3-year OS than patients staged by MRI alone (85.5% vs. 60.4%, P = 0.006; adjusted HR = 0.34, P = 0.005). CONCLUSION: PET/CT more accurately detected and staged recurrence of nasopharyngeal carcinoma and accordingly complemented MRI, providing benefit in contouring and OS.


Asunto(s)
Neoplasias Nasofaríngeas , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Fluorodesoxiglucosa F18 , Carcinoma Nasofaríngeo/diagnóstico por imagen , Carcinoma Nasofaríngeo/terapia , Terapia Recuperativa , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/terapia , Recurrencia Local de Neoplasia/patología , Imagen por Resonancia Magnética , Sensibilidad y Especificidad , Neoplasias Nasofaríngeas/diagnóstico por imagen , Neoplasias Nasofaríngeas/terapia , Estadificación de Neoplasias
18.
FASEB J ; 36(6): e22361, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35616366

RESUMEN

Loss of FXR, one of bile acid receptors, enlarged livers. Yes-associated protein 1 (YAP1), a dominant oncogene, promotes hepatocellular carcinoma (HCC). However, the relationship between FXR and YAP1 was unspecified in bile acid homeostasis in HCC. Here, we used TIMER2.0, the Cancer Genome Atlas (TCGA) Database, and Kaplan-Meier Plotter Database and discovered that FXR was positively correlated with better prognosis in liver cancer patients. Our previous research showed that dihydroartemisinin (DHA) inhibited cell proliferation in HepG2 and HepG22215 cells. However, the relationship of YAP1 and the bile acid receptor FXR remains elusive during DHA treatment. Furthermore, we showed that DHA improved FXR and reduced YAP1 in the liver cancer cells and mice. Additionally, the expression of nucleus protein FXR was enhanced in Yap1LKO mice with liver cancer. DHA promoted the expression level of whole and nuclear protein FXR independent of YAP1 in Yap1LKO mice with liver cancer. DHA declined cholesterol 7α-hydroxylase, but not sterol 27-hydroxylase, and depressed cholic acid and chenodeoxycholic acid of liver tissue in Yap1LKO mice with liver cancer. Generally, our results suggested that DHA improved FXR and declined YAP1 to suppress bile acid metabolism. Thus, we suggested that FXR acted as a potential therapeutic target in HCC.


Asunto(s)
Artemisininas , Carcinoma Hepatocelular , Neoplasias Hepáticas , Animales , Artemisininas/farmacología , Ácidos y Sales Biliares/metabolismo , Carcinoma Hepatocelular/metabolismo , Colesterol 7-alfa-Hidroxilasa/metabolismo , Humanos , Hígado/metabolismo , Neoplasias Hepáticas/metabolismo , Ratones , Proteínas Señalizadoras YAP
19.
Nanotechnology ; 35(1)2023 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-37774685

RESUMEN

Interactions between ultrafast lasers and metal targets are crucial in various laser micro/nano-machinings. However, the underlying incubation and absorption-enhancement mechanisms remain elusive, which hinders the quality control of laser processing. Herein, we studied the incubation effect and absorption enhancement during multi-shot femtosecond-laser ablations via combining experiments and hydrodynamic simulations, taking aluminum alloy and stainless steels as paradigm materials. Accumulation effects of heat and damage-induced deformation were revealed by the evolutions of microstructures induced by low-energy femtosecond lasers. The calculated ablation thresholds were reduced with shot number, demonstrating the incubation effect. Calculation of threshold fluence via crater diameter is better than ablation depth, because that the latter is determined by different parameters at low- and high-energy conditions. Experimental observations and hydrodynamic simulations indicated that the enhanced absorption could be attributed to several factors, including laser-induced surface micro/sub-micro structures, photoionization, and plasma evolutions.

20.
Lipids Health Dis ; 22(1): 21, 2023 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-36747216

RESUMEN

BACKGROUND: The Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE) index has been recommended as an ideal indicator of body fat and exhibited significant correlation with cardiometabolic risk factors. However, whether the CUN-BAE index correlates with incident diabetes in Asian populations is unknown. Therefore, this longitudinal study was designed to evaluate the association between baseline CUN-BAE index and type 2 diabetes mellitus (T2DM). METHODS: This retrospective longitudinal study involved 15,464 participants of 18-79 years of age in the NAGALA (NAfld in the Gifu Area Longitudinal Analysis) study over the period of 2004-2015. Cox proportional hazards regression was performed to test the relationship between the baseline CUN-BAE index and diabetes incidence. Further stratification analysis was conducted to ensure that the results were robust. The diagnostic utility of the CUN-BAE index was tested by the receiver operating characteristic (ROC) curve. RESULTS: Over the course of an average follow-up of 5.4 years, 373 (2.41%) participants developed diabetes. A higher diabetes incidence was associated with higher CUN-BAE quartiles (P for trend< 0.001). Each 1 unit increase in CUN-BAE index was associated with a 1.08-fold and 1.14-fold increased risk of diabetes after adjustment for confounders in males and females, respectively (both P < 0.001). Stratification analysis demonstrated a consistent positive correlation between baseline CUN-BAE and diabetes incidence. Moreover, based on ROC analysis, CUN-BAE exhibited a better capacity for diabetes prediction than both body mass index (BMI) and waist circumference (WC) in both sexes. CONCLUSIONS: The baseline CUN-BAE level was independently related to the incidence of diabetes. Increased adiposity determined by CUN-BAE could be used as a strong nonlaboratory predictor of incident diabetes in clinical practice.


Asunto(s)
Adiposidad , Diabetes Mellitus Tipo 2 , Masculino , Femenino , Humanos , Estudios Retrospectivos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Estudios Longitudinales , Obesidad/metabolismo , Índice de Masa Corporal , Circunferencia de la Cintura , Tejido Adiposo/metabolismo , Factores de Riesgo
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