Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 69
Filtrar
Más filtros













Base de datos
Intervalo de año de publicación
1.
J Phys Chem Lett ; : 5445-5451, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38747537

RESUMEN

The catalytic activity of transition-metal-based atomically dispersed catalysts is closely related to the spin states. Manipulating the spin state of metal active centers could directly adjust the d orbital occupancy and optimize the adsorption behavior and electron transfer of the intermediates and transition metals, which would enhance the catalytic activity. We summarize the means of manipulating spin states and the spin-related catalytic descriptors. In future work, we will build a quantifiable and accurate prediction intelligent model through artificial intelligence (AI) and machine learning tools. Furthermore, we will develop new spin regulation methods to carry out the directional regulation of atomically dispersed catalysts through this model, providing new insight into the rational design of transition-metal-based atomically dispersed catalysts through spin manipulation.

2.
Brain Struct Funct ; 2024 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-38703218

RESUMEN

ß-synuclein, a member of the synuclein family, is frequently co-expressed with α-synuclein in the neural system, where it serves to inhibit abnormal aggregation of α-synuclein in neurodegenerative diseases. Beyond its role in pathological conditions, ß-synuclein plays various functions independently of α-synuclein. In our investigation, we discovered a broader expression of ß-synuclein in the mouse retina compared to α-synuclein. This widespread pattern implies its potential significance in the retina. Through detailed examination via light- and electron-microscopic immunocytochemistry, we identified ß-synuclein expression from the inner segment (IS) and outer segment (OS) of photoreceptor cells to the ganglion cell layer (GCL). Our findings unveiled unique features, including ß-synuclein immunoreactive IS and OS of cones, higher expression in cone pedicles than in rod spherules, absence in horizontal cells, limited expression in cone bipolar dendrites and somas, higher expression in cone bipolar terminals, presence in most amacrine cells, and expression in almost majority of somas in GCL with an absence in intrinsically photosensitive retinal ganglion cell (ipRGCs) processes. Notably, all cholinergic amacrine cells express high ß- but not α-synuclein, while dopaminergic amacrine cells express α-synuclein exclusively. These distinctive expression patterns offer valuable insights for further exploration into the functions of ß-synuclein and its potential role in synuclein pathology within the retina.

3.
J Colloid Interface Sci ; 666: 371-379, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38603879

RESUMEN

VO2 (B) is recognized as a promising cathode material for aqueous zinc metal batteries (AZMBs) owing to its remarkable specific capacity and its unique, expansive tunnel structure, which facilitates the reversible insertion and extraction of Zn2+. Nonetheless, challenges such as the inherent instability of the VO2 structure, poor ion/electron transport and a limited capacity due to the low redox potential of the V3+/V4+ couple have hindered its wider application. In this study, we present a strategy to replace vanadium ions by doping Al3+ in VO2. This approach activates the multi-electron reaction (V4+/V5+), to increase the specific capacity and improve the structural stability by forming robust V5+O and Al3+O bonds. It also induces a local electric field by altering the local electron arrangement, which significantly accelerates the ion/electron transport process. As a result, Al-doped VO2 exhibits superior specific capacity, improved cycling stability, and accelerated electronic transport kinetics compared to undoped VO2. The beneficial effects of heterogeneous atomic doping observed here may provide valuable insights into the improvement electrode materials in metal-ion battery systems other than those based on Zn.

4.
Cancer Lett ; 589: 216825, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38548218

RESUMEN

As one of the key metabolic enzymes in the glycolytic pathway, lactate dehydrogenase A (LDHA) might be linked to tumor proliferation by driving the Warburg effect. Circular RNAs (circRNAs) are widely implicated in tumor progression. Here, we report that circTATDN3, a circular RNA that interacts with LDHA, plays a critical role in proliferation and energy metabolism in CRC. We found that circTATDN3 expression was increased in CRC cells and tumor tissues and that high circTATDN3 expression was positively associated with poor postoperative prognosis in CRC patients. Additionally, circTATDN3 promoted the proliferation of CRC cells in vivo and vitro. Mechanistically, circTATDN3 was shown to function as an adaptor molecule that enhances the binding of LDHA to FGFR1, leading to increased LDHA phosphorylation and consequently promoting the Warburg effect. Moreover, circTATDN3 increased the expression of LDHA by sponging miR-511-5p, which synergistically promoted CRC progression and the Warburg effect. In conclusion, circTATDN3 may be a target for the treatment of CRC.


Asunto(s)
Neoplasias Colorrectales , MicroARNs , Humanos , ARN Circular/genética , Línea Celular Tumoral , Lactato Deshidrogenasa 5/genética , Lactato Deshidrogenasa 5/metabolismo , Neoplasias Colorrectales/patología , Proliferación Celular , MicroARNs/genética , MicroARNs/metabolismo , Regulación Neoplásica de la Expresión Génica
5.
Cancer Lett ; 592: 216761, 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38490326

RESUMEN

Hepatocellular carcinoma (HCC) is a highly aggressive malignant tumor with limited treatment options and poor prognosis. In this study, we reveal the pivotal role of Stratifin (SFN), also recognized as 14-3-3σ, in driving HCC progression. Our investigation underscores a substantial upregulation of SFN within HCC tissues, manifesting a significant association with worse prognostic outcomes among HCC patients. In vitro and in vivo experiments reveal that SFN overexpression significantly amplifies proliferation, mitigates sorafenib-induced effects on HCC cells, and enhances tumorigenesis. While SFN silencing exerts converse effects on HCC progression. Additionally, we unveil a critical interaction between SFN and AKT, where SFN boosts AKT kinase activity by disrupting the binding of PHLPP2 and AKT, thereby intensifying the malignant progression of HCC cells. In conclusion, this study identifies the oncogenic role of SFN and elucidates the regulatory mechanism of the SFN/AKT axis in HCC, which may provide valuable insights into the mechanisms of HCC progression and potential targets for therapeutic intervention.

6.
J Gastroenterol Hepatol ; 39(5): 908-919, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38323685

RESUMEN

BACKGROUND AND AIM: A growing number of studies have demonstrated that neoadjuvant chemotherapy can improve the prognosis of patients with resectable colorectal liver metastases (CRLM). However, the routine use of postoperative adjuvant chemotherapy (POAC) for patients with CRLM after simultaneous resection remains controversial. This retrospective study investigated the impact of POAC on outcomes in patients with CRLM who underwent simultaneous resection of colorectal cancer tumors and liver metastases using propensity score matching (PSM) analysis. METHODS: From January 2009 to November 2020, patients with CRLM who underwent simultaneous resection were retrospectively enrolled. The confounding factors and selection bias were adjusted by 2:1 PSM. Patients were stratified into the POAC and non-POAC groups. Kaplan-Meier curves were utilized to compare overall survival (OS) and progression-free survival (PFS) between the groups. Univariate and multivariate Cox regression analyses were used to identify independent clinicopathological factors before and after PSM analysis. The utility of the model was evaluated using receiver operating characteristic (ROC) and calibration curves after PSM analysis. RESULTS: In total, 478 patients with resectable CRLM were enrolled and assigned to the POAC (n = 212, 60.9%) or non-POAC group (n = 136, 39.1%). After 2:1 PSM, there was no significant bias between the groups. Kaplan-Meier survival analysis revealed a significant effect of POAC on OS (P < 0.001) but not PFS. Multivariate Cox regression analysis identified T stage (T3-T4), lymph node metastasis, radiofrequency ablation during surgery, operative time ≥ 325 min, and the receipt of postoperative adjuvant chemotherapy (hazard ratio = 0.447, 95% confidence interval = 0.312-0.638, P < 0.001) as independent prognostic factors for OS. The areas under the ROC curves for the nomogram model for predicting 1-, 3-, and 5-year survival were 0.653, 0.628, and 0.678, respectively. Subgroups analysis suggested that POAC can enhance OS in patients with resectable CRLM with either low (1-2, P < 0.001) or high clinical risk scores (3-5, P = 0.020). CONCLUSIONS: Overall, this study identified POAC as a prognostic factor to predict OS in patients with CRLM undergoing simultaneous resection.


Asunto(s)
Neoplasias Colorrectales , Hepatectomía , Neoplasias Hepáticas , Humanos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/mortalidad , Quimioterapia Adyuvante , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/terapia , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Puntaje de Propensión , Tasa de Supervivencia , Factores de Tiempo , Resultado del Tratamiento
7.
J Colloid Interface Sci ; 659: 267-275, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38176236

RESUMEN

Vanadium-based materials are widely recognized as the primary candidate cathode materials for aqueous Zn-ion batteries (AZIBs). However, slow kinetics and poor stability pose significant challenges for widespread application. Herein, to address these issues, alkali metal ions and polyaniline (PANI) are introduced into layered hydrated V2O5 (VO). Density functional theory calculations reveal that the synthesized (C6H4NH)0.27K0.24V2O5·0.92H2O (KPVO), with K+ and PANI co-intercalation, exhibits a robust interlayer structure and a continuous three-dimensional (3D) electron transfer network. These properties facilitate the reversible diffusion of Zn2+ with a low migration potential barrier and rapid response kinetics. The KPVO cathode exhibits a discharge specific capacity of 418.3 mAh/g at 100 mA/g and excellent cycling stability with 89.5 % retention after 3000 cycles at 5 A/g. This work provides a general strategy for integrating cathode materials to achieve high specific capacity and excellent kinetic performance.

8.
Biochim Biophys Acta Mol Cell Res ; 1871(2): 119620, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-37926157

RESUMEN

Fibroblast growth factor 21 (FGF21) is a key regulator of energy metabolism. Recent studies suggested that serum FGF21 levels increase with declining renal function. However, the link between FGF21 and kidney diseases and the direct effect of FGF21 in renal fibrosis remains unclear. In this study, FGF21 was upregulated in unilateral ureteral obstruction (UUO)-induced renal fibrosis and cellular fibrosis induced by transforming growth factor-ß, and renal expression of FGF21 was positively correlated with fibrosis markers. Additionally, FGF21 was regulated by Wnt/ß-catenin signaling pathway. The knockdown and overexpression of FGF21 in mouse tubular epithelial cells demonstrated that FGF21 alleviates renal fibrosis by inhibiting the Wnt/ß-catenin signaling pathway. To investigate the effect of FGF21 on renal fibrosis in vivo, we established an overexpression model by injecting the plasmid in mice and found that FGF21 overexpression relieved UUO-induced renal fibrosis and renal inflammatory response. Taken together, FGF21 is upregulated with the activation of Wnt/ß-catenin signaling pathway and alleviates renal fibrosis by inhibiting the activation of Wnt/ß-catenin signaling pathway in a negative feedback mode. These results provide a new understanding for the source of elevated serum FGF21 in patients with chronic kidney disease and prove that FGF21 is a direct inhibitor of the progression of renal fibrosis, thus providing novel therapeutic intervention insights for renal fibrosis.


Asunto(s)
Factores de Crecimiento de Fibroblastos , Enfermedades Renales , Obstrucción Ureteral , Humanos , Ratones , Animales , Obstrucción Ureteral/complicaciones , Obstrucción Ureteral/metabolismo , Vía de Señalización Wnt , Enfermedades Renales/genética , Enfermedades Renales/metabolismo , Fibrosis
9.
PeerJ ; 11: e16424, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38077439

RESUMEN

Purpose: Optimal serological biomarkers have been absent for the early diagnosis of endometrial cancer, to date. In this study, we aimed to define the diagnostic performances of individual and combined detection of serum cysteine protease inhibitor 1 (CST1) with traditional tumor markers, including glycated antigen 125 (CA125) and human epididymis protein 4 (HE4), in patients with early-stage endometrial cancer (EC). Methods: The performances of individual and combined detection of serum CST1, HE4, and CA125 were evaluated by enzyme-linked immunosorbent assay (ELISA) and chemiluminescent immunoassay, respectively. A training data set of 67 patients with early EC, 67 patients with endometrial benign lesion (EBL), and 67 healthy controls (HC) was used to develop a predictive model for early EC diagnosis, which was validated by an independent validation data set. Results: In the training data set, serum CST1 and HE4 levels in the early EC group were significantly higher than in EBL/HC groups (P < 0.05), while there was no significant difference of serum CA125 level between the early EC and EBL/HC groups (P > 0.05). Serum CST1 and HE4 exhibited areas under the curve (AUC) of 0.715 with 31.3% sensitivity at 90.3% specificity, and 0.706 with 23.9% sensitivity at 95.5% specificity, respectively. Combined detection of serum CST1 and HE4 exhibited an AUC of 0.788 with 49.3% sensitivity at 92.5% specificity. The combination of serum CST1 and HE4 showed promise in diagnosis. Conclusion: CST1 is a prospective serological biomarker for early EC diagnosis, and the combination of CST1 and HE4 contributes to the further improvement in the diagnosis of patients with early-stage EC.


Asunto(s)
Neoplasias Endometriales , Proteínas , Femenino , Humanos , Antígeno Ca-125 , Detección Precoz del Cáncer , Neoplasias Endometriales/diagnóstico , Estudios Prospectivos , Proteínas/análisis
10.
Brain Struct Funct ; 228(7): 1703-1724, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37481742

RESUMEN

Substance P (SP), a neuroprotective peptidergic neurotransmitter, is known to have immunoreactivity (IR) localized to amacrine and/or ganglion cells in a variety of species' retinas, but it has not yet been studied in the mouse retina. Thus, we investigated the distribution and synaptic organization of SP-IR by confocal and electron microscopy immunocytochemistry in the mouse retina. SP-IR was distributed in the inner nuclear layer (INL), inner plexiform layer (IPL), and ganglion cell layer (GCL). Most of the SP-IR somas belonged to amacrine cells (2.5% of all) in the INL and their processes stratified into the S1, S3, and S5 layers of the IPL, with the most intense band in the S5 layer. Some SP-IR somas can also be observed in the GCL, which were identified as displaced amacrine cells (82%, 1269/1550) and ganglion cells (18%, 281/1550) by antibodies against AP2α and RBPMS, respectively. Such SP-IR ganglion cells (1.2% of all RGCs) can be further divided into 3 subgroups expressing SP/α-Synuclein (α-Syn), SP/GAD67, and/or SP/GAD67/α-Syn. Possible physiological and pathological roles of these ganglion cells are discussed. Further, electron microscopy evidence demonstrates that SP-IR amacrine cells receive major inputs from other SP-IR amacrine cell processes (146/242 inputs) and output mostly to SP-negative amacrine cell processes (291/673 outputs), suggesting series inhibition among amacrine cells. These results reveal for the first time an explicit distribution, novel ganglion cell features, and synaptic organization of SP-IR in the mouse retina, which is important for the future use of mouse models to study the roles of SP in healthy and diseased (including Parkinson's disease) retinal states.


Asunto(s)
Retina , Sustancia P , Animales , Ratones , Sustancia P/análisis , Retina/química , Células Amacrinas , Microscopía Electrónica , Neurotransmisores
11.
J Mol Model ; 29(6): 172, 2023 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-37160616

RESUMEN

CONTEXT: While Au-based catalysts recently have shown tremendous potential in glucose oxidation to gluconic acid, the detailed reaction mechanism is still unclear, which impedes the development of direct glucose fuel cell (DGFC). METHODS: Using density functional theory (DFT), we exhibit some new adsorption configurations and oxidation mechanisms by considering both the open chain form and the ring form of glucose on Au(111) surface in the presence of OH. The strong interactions between glucose and the OH adsorbed surface are obtained. Moreover, form the calculated energy pathways, the oxidation of glucose in the open chain involves the dissociation of the formyl C - H bond by the adsorbed OH, while the ring form glucose oxidation is initiated by O - H bond rupture rather than C - H bond scission and preferentially undergoes the ring-open process to generate the open chain form glucose. Meanwhile, the results demonstrate that the adsorbed OH assists in reducing the activation energy of reaction process.

12.
J Phys Chem Lett ; 14(20): 4760-4765, 2023 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-37184776

RESUMEN

The adsorption energy of adsorbed molecules on single-atom catalysts is a key indicator of the catalytic activity of the catalysts. Developing a generic and interpretable structure-property prediction model from numerous influencing factors is a challenging task. In this work, we constructed a machine learning (ML) model from first-principles calculations of the adsorption energy data of O2 on Ni(II), Co(II), Cu(II), Fe(II), Fe(III), and Mn(II) single-atom catalysts supported on 15 different N-C substrates under various spin states. A mathematic formula is proposed to predict the adsorption energy by a novel data-driven descriptor derived from physically meaningful factors such as geometric distances and atomic charges. This data-driven descriptor is relevant to only the geometrical configuration of the adsorbate, while the parameters in the linear formulas contain only substrate-specific information. This ML model with the ability to decouple variables will greatly advance the understanding of metal-N-C single-atom catalysts and help in the design of new substrates to modulate catalytic activity.

13.
J Comp Neurol ; 531(10): 1057-1079, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37002599

RESUMEN

α-Synuclein (α-Syn) is enriched in presynaptic terminals of the central nervous system including the retina and plays a role in the synaptic vesicle cycle and synaptic transmission. Abnormal aggregation of α-Syn is considered to be the main component of the Lewy bodies that are the pathological hallmarks of Parkinson's disease. Although expression pattern of α-Syn has been described in the retinas, its precise cellular and subcellular locations are poorly understood. We investigated the precise expression of α-Syn using light microscopy (LM) and electron microscopy (EM) with antibodies against α-Syn in the mouse retina. We found that the majority of α-Syn immunoreactivity (IR) is located in GABAergic, glycinergic, and dopaminergic amacrine cells, and their processes often make a direct synapse to other labeled or unlabeled amacrine profiles, bipolar cell terminals, or ganglion cell dendrites. Further, our LM and immuno-EM results confirm the absence of α-Syn in excitatory photoreceptors, bipolar cell bodies, and their ribbon synapses, providing evidence, for the first time, that ribbon synapses do not express α-Syn. Additionally, α-Syn IR is located in the ganglion cells, some of which are intrinsically photosensitive retinal ganglion cells. These results reveal a previously unappreciated inhibitory synapse-specific expression pattern of α-Syn in the retina, suggesting that α-Syn may play a distinct role in the modulation and integration of inhibitory synaptic transmission in the retina.


Asunto(s)
Retina , alfa-Sinucleína , Animales , Ratones , Retina/fisiología , Células Ganglionares de la Retina/metabolismo , Terminales Presinápticos/metabolismo , Sinapsis/ultraestructura
14.
J Comp Neurol ; 531(11): 1184-1197, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37073449

RESUMEN

The light pathways are segregated into rod and cone pathways in which rods synapse with rod bipolar cells (RBCs), while cones contact cone bipolar cells (CBCs). However, previous studies found that cones can make synapse with RBCs (cone-RBC synapses) and rods can contact OFF CBC in primate and rabbit retinas. Recently, such cone-RBC synapses have been reported physiologically and morphologically in the mouse retina. Nevertheless, the precise subcellular evidence to determine whether it is the invaginating synapse or the flat contact remains absent. This is due to a lack of immunochemically verified ultrastructural data. Here, we investigated the precise expression of protein kinase C alpha (PKCα) using pre-embedding immunoelectron microscopy (immuno-EM) with a monoclonal antibody against PKCα, a biomarker for the RBCs. We determined the nanoscale localization of PKCα in the outer plexiform layer of the mouse and guinea pig retinas. Our results demonstrate the existence of both the direct invaginating synapse and the basal/flat contact of the cone-RBCs, providing for the first time immunochemically verified ultrastructural evidence for the cone-RBC synapse in the mouse and guinea pig retinas. These results suggest that the cross talk between cone and rod pathways is much more extensive than previously assumed.


Asunto(s)
Proteína Quinasa C-alfa , Células Fotorreceptoras Retinianas Conos , Cobayas , Ratones , Animales , Conejos , Células Fotorreceptoras Retinianas Conos/fisiología , Retina/fisiología , Células Bipolares de la Retina , Sinapsis/ultraestructura , Células Fotorreceptoras
15.
J Environ Manage ; 335: 117590, 2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-36863145

RESUMEN

Straw returning is suggested as a sustainable agricultural practice to promote soil organic carbon (SOC) sequestration, whose magnitude can be influenced by climatic, edaphic and agronomic factors simultaneously. However, the driving factors regulating straw returning-induced SOC increase in China's uplands remain uncertain. This study conducted a meta-analysis by collecting data from 238 trials at 85 field sites. The results showed that straw returning significantly increased SOC content by an average of 16.1% ± 1.5% with an average sequestration rate of 0.26 ± 0.02 g kg-1 yr-1. The improvement effects were significantly better in the northern China (NE-NW-N) than in the eastern and central (E-C). SOC increases were more pronounced in C-rich and alkaline soils, in cold and dry climates, and under larger amounts of straw-C and moderate nitrogen fertilizer inputs. Longer experimental period resulted in higher SOC increase rates but lower SOC sequestration rates. Furthermore, partial correlation analysis and structural equation modelling revealed that total straw-C input was the key driving factor of SOC increase rate whereas straw returning duration was the dominant limiting factor of SOC sequestration rate across China. Climate conditions were potential limiting factors of SOC increase rate in NE-NW-N and SOC sequestration rate in E-C. It was suggested that straw returning with large application amounts should be more strongly recommended in uplands in NE-NW-N especially in the straw applications at the beginning, from the perspective of SOC sequestration.


Asunto(s)
Carbono , Suelo , Suelo/química , Carbono/análisis , Secuestro de Carbono , Productos Agrícolas , Agricultura/métodos , China
16.
Angew Chem Int Ed Engl ; 62(18): e202301925, 2023 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-36866977

RESUMEN

Spin manipulation of transition-metal catalysts has great potential in mimicking enzyme electronic structures to improve activity and/or selectivity. However, it remains a great challenge to manipulate room-temperature spin state of catalytic centers. Herein, we report a mechanical exfoliation strategy to in situ induce partial spin crossover from high-spin (s=5/2) to low-spin (s=1/2) of the ferric center. Due to spin transition of catalytic center, mixed-spin catalyst exhibits a high CO yield of 19.7 mmol g-1 with selectivity of 91.6 %, much superior to that of high-spin bulk counterpart (50 % selectivity). Density functional theory calculations reveal that low-spin 3d-orbital electronic configuration performs a key function in promoting CO2 adsorption and reducing activation barrier. Hence, the spin manipulation highlights a new insight into designing highly efficient biomimetic catalysts via optimizing spin state.

17.
J Org Chem ; 88(7): 4494-4503, 2023 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-36972416

RESUMEN

The mechanism of the rhodium-catalyzed C-H alkenylation/directing group migration and [3+2] annulation of N-aminocarbonylindoles with 1,3-diynes has been investigated with DFT calculations. On the basis of mechanistic studies, we mainly focus on the regioselectivity of 1,3-diyne inserting into the Rh-C bond and the N-aminocarbonyl directing group migration involved in the reactions. Our theoretical study uncovers that the directing group migration undergoes a stepwise ß-N elimination and isocyanate reinsertion process. As studied in this work, this finding is also applicable to other relevant reactions. Additionally, the role of Na+ versus Cs+ involved in the [3+2] cyclization reaction is also probed.

18.
J Cancer Res Clin Oncol ; 149(10): 6901-6916, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36826593

RESUMEN

PURPOSE: The crucial role of N6-methyladenosine (m6A) methylation in anti-tumor immunity and immunotherapy has been broadly depicted. However, the molecular phenotypic linkages between m6A modification pattern and immunological ecosystem are expected to be disentangled in hepatocellular carcinoma (HCC), for immunotherapeutic unresponsiveness circumvention and combination with promising drug agents. METHODS: Modification patterns of m6A methylation were qualitatively dissected according to the large-scale HCC samples profiling. We then determined the immune phenotypic linkages by systematically evaluating their tumor microenvironment composition, immune/stromal-relevant signature, immune checkpoints correlation, and prognostic value. Individual quantification of m6A methylation pattern was achieved by m6Ascore construction, intensified by longitudinal single-cell analysis of immunotherapy cohort and validated by the transcriptomic profiles of our in-hospital GDPH-HCC cohort. Candidate therapeutic agents were also screened out. RESULTS: Three distinct m6A methylation patterns were determined in high accordance with inflamed-, excluded-, and desert-immunophenotype. To be precise, Immune-inflamed high-m6Ascore group was characterized by activated immunity with favorable prognosis. Stromal activation and absence of immune cell infiltration were observed in low-m6Ascore phenotype, linked to impaired outcome. Patients with low-m6Ascore demonstrated diminished responses and clinical benefits for cohorts receiving immunotherapy. The above credible linkage between m6A methylation pattern and tumor immune microenvironment was robustly validated in our GDPH-HCC cohort. Single-cell dynamic change of m6A methylation level in exhausted CD8 T cell and fibroblast was depicted in immunotherapy cohort fore and art. Derived from m6A methylation pattern, seven potential frontline drug agents were recognized as promising choice for high-m6Ascore patients. CONCLUSION: Our work bridged the credible linkage between epigenetics and anti-tumor immunity in HCC, unraveling m6A modification pattern as immunological indicator and predictor for immunotherapy. Individualized m6Ascore facilitated strategic choices to maximize therapy-responsive possibility.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Metilación , Carcinoma Hepatocelular/genética , Ecosistema , Neoplasias Hepáticas/genética , Microambiente Tumoral , Fenotipo
19.
BMC Pediatr ; 23(1): 19, 2023 01 13.
Artículo en Inglés | MEDLINE | ID: mdl-36639749

RESUMEN

BACKGROUND: The hemolytic nature of hemolytic disease of the newborn (HDN) is described as the abnormal destruction and decomposition of red blood cells, causing heterogeneous manifestations such as abnormal red blood cell volume and morphology. Mean corpuscular volume (MCV) and red blood cell volume distribution width (RDW) are commonly used parameters related to red blood cell volume. Total serum bilirubin (TSB) is routinely monitored among newborns. This study aims to explore the value of MCV and RDW, combined with TSB, to improve the efficiency of HDN diagnosis. METHODS: Three hundred eighty-eight children with HDN and 371 children with non-HDN pathological jaundice who were diagnosed and treated in the neonatal department of our hospital from January 2019 to December 2020 were included in the study. Clinical data collected include examination results of laboratory indicators, such as MCV, coefficient of variation of red blood cell volume distribution width (RDW-CV), standard deviation of red blood cell volume distribution width (RDW-SD), and TSB. The differences in the indicators between the two groups of children were retrospectively analyzed. RESULTS: 1) The detection rate of HDN in children in the early group was higher than that in the late group (P < 0.001). 2) The early-stage group had lower TSB levels and higher values of MCV, RDW-CV and RDW-SD (P < 0.001). Compared with the children in the non-HDN group, the indices in the HDN group were higher in the early stage (P < 0.001). 3) In the early stage, the TSB, MCV, RDW-CV, and RDW-SD were positively correlated with the diagnosis of HDN (P < 0.001). Early monitoring of TSB, MCV, RDW-CV and RDW-SD was valuable for HDN detection, the area under the curve (AUC) was 0.729, 0.637, 0.715, and 0.685, respectively (P < 0.001). 4) After a binary logistic analysis at TSB > 163.3 µmol/L, MCV > 96.35fL, and RDW-CV > 16.05%, the diagnosis rate of HDN increased (P < 0.001). The AUC of the HDN detected using the combined indicators was 0.841. CONCLUSION: At MCV > 96.35fL or RDW-CV > 16.05%, children with jaundice in three days of birth (especially children with TSB > 163.3 µmol/L) should be screened for HDN. A combination of TSB, MCV, and RDW-CV can improve the early detection rate of HDN, contribute to reduce the readmission rate and risk of hyperbilirubinemia.


Asunto(s)
Índices de Eritrocitos , Ictericia , Niño , Humanos , Recién Nacido , Estudios Retrospectivos , Eritrocitos , Ictericia/diagnóstico , Bilirrubina
20.
Analyst ; 147(11): 2549-2557, 2022 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-35546319

RESUMEN

The group specific assay of total aflatoxins (AFs) often requires specific antibodies. A controllable staining colorimetric method was proposed to determine AFs by exploiting controllable electrostatic-staining of carboxylated cellulose membranes (CCMs) with Hg2+-capped gold nanoparticles (AuNPs). Under electrostatic force, Hg2+ connects AuNPs and CCMs like a bridge, causing CCMs to be stained by AuNPs. The two adjacent carbonyl groups in the AF structure can chelate Hg2+. When AFs are present, Hg2+ and AFs will form complexes, which reduces the attachment of AuNPs on the CCMs. Therefore, the different degrees of electrostatic-staining of CCMs show different color changes. Based on this phenomenon, a naked-eye colorimetric detection assay of AFs was designed. The visual limit of detection (VLOD) reached 10 ppb, which makes it easily and effectively complete the early-warning and semi-quantitative detection of AFs. To our knowledge, this is the first method for colorimetric detection of AFs based on the controllable electrostatic-staining mechanism, which can be used for the determination of AFs in actual water samples such as beer and beverages. Besides, the colorimetric sensing method based on the controllable electrostatic-staining mechanism provides a novel methodology for early-warning and semi-quantitative detection of toxic and hazardous substances.


Asunto(s)
Aflatoxinas , Mercurio , Nanopartículas del Metal , Aflatoxinas/análisis , Ácidos Carboxílicos , Celulosa , Colorimetría/métodos , Oro/química , Nanopartículas del Metal/química , Coloración y Etiquetado , Agua
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA