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2.
Sci Rep ; 14(1): 23161, 2024 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-39369023

RESUMEN

To explore the influence of surfactant concentration on the pore structure and permeability of coal samples during the chemical enhancement of coalbed methane production, different kinds and different concentrations of surfactants were added to the chemical solution, and the coal samples were soaked. Methods such as low-field nuclear magnetic resonance testing (NMR), fractal theory, permeability testing, surface tension testing, and contact angle testing were employed to analyze the variation patterns of coal sample pore structure, fractal characteristics, and permeability, and to explore the correlation between surface tension, contact angle, and the degree of pore structure development. The results show that the increase in total porosity of coal samples, the increase in the seepage pore porosity, the decrease in Dt, and the growth rate of permeability increase with the increase in surfactant concentration, and are negatively correlated with the surface tension of the solution and the contact angle of the coal-solution interface, while the decrease in Ds is not significantly correlated with surfactant concentration, surface tension, or contact angle. In terms of the erosion effect of a chemical solution on coal samples, the influence of contact angle is greater than that of surface tension, while surface tension has the greatest impact on the development of adsorption pores. By adding different surfactants, the surface tension of the chemical solution and the contact angle of the coal-solution interface can be controlled, further promoting the erosion of coal samples, which is of positive significance for the chemical enhancement of coalbed methane production.

3.
Front Neurorobot ; 18: 1452019, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39381775

RESUMEN

Introduction: Currently, using machine learning methods for precise analysis and improvement of swimming techniques holds significant research value and application prospects. The existing machine learning methods have improved the accuracy of action recognition to some extent. However, they still face several challenges such as insufficient data feature extraction, limited model generalization ability, and poor real-time performance. Methods: To address these issues, this paper proposes an innovative approach called Swimtrans Net: A multimodal robotic system for swimming action recognition driven via Swin-Transformer. By leveraging the powerful visual data feature extraction capabilities of Swin-Transformer, Swimtrans Net effectively extracts swimming image information. Additionally, to meet the requirements of multimodal tasks, we integrate the CLIP model into the system. Swin-Transformer serves as the image encoder for CLIP, and through fine-tuning the CLIP model, it becomes capable of understanding and interpreting swimming action data, learning relevant features and patterns associated with swimming. Finally, we introduce transfer learning for pre-training to reduce training time and lower computational resources, thereby providing real-time feedback to swimmers. Results and discussion: Experimental results show that Swimtrans Net has achieved a 2.94% improvement over the current state-of-the-art methods in swimming motion analysis and prediction, making significant progress. This study introduces an innovative machine learning method that can help coaches and swimmers better understand and improve swimming techniques, ultimately improving swimming performance.

4.
Prog Neurobiol ; 241: 102670, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39366505

RESUMEN

To encode allocentric space information of a viewing object, it is important to relate perceptual information in the first-person perspective to the representation of an entire scene which would be constructed before. A substantial number of studies investigated the constructed scene information (e.g., cognitive map). However, only few studies have focused on its influence on perceptual processing. Therefore, we designed a visually guided saccade task requiring monkeys to gaze at objects in different locations on different backgrounds clipped from large self-designed mosaic pictures (parental pictures). In each trial, we presented moving backgrounds prior to object presentations, indicating a frame position of the background image on a parental picture. We recorded single-unit activities from 377 neurons in the posterior inferotemporal (PIT) cortex of two macaques. Equivalent numbers of neurons showed space-related (119 of 377) and object-related (125 of 377) information. The space-related neurons coded the gaze locations and background images jointly rather than separately. These results suggest that PIT neurons represent a particular location within a particular background image. Interestingly, frame positions of background images on parental pictures modulated the space-related responses dependently on parental pictures. As the frame positions could be acquired by only preceding visual experiences, the present results may provide neuronal evidence of a mnemonic effect on current perception, which might represent allocentric object location in a scene beyond the current view.


Asunto(s)
Neuronas , Percepción Espacial , Lóbulo Temporal , Animales , Lóbulo Temporal/fisiología , Percepción Espacial/fisiología , Masculino , Neuronas/fisiología , Movimientos Sacádicos/fisiología , Estimulación Luminosa/métodos , Percepción Visual/fisiología , Macaca , Macaca mulatta
5.
Molecules ; 29(18)2024 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-39339492

RESUMEN

Bioremediation of acid mine drainage (AMD) was often challenged by poor tolerance of sulfate-reducing bacteria (SRB) to heavy metals and low bioactivity. The highly active immobilized particles with Fe0/Fe2+ enhanced SRB (Fe0/2+-SRB) were prepared by the microorganism immobilization technique. Three dynamic columns were constructed to investigate the adsorption capacity of Fe0/2+-SRB for Mn2+ under varying adsorption layer heights, inflow velocity, and initial Mn2+ concentrations. The role of each matrix material in the immobilized particles was explored, the mechanism of AMD remediation by Fe0/2+-SRB was revealed, and the adaptability of Fe0/2+-SRB to AMD under various initial conditions was investigated. The results showed that the prepared Fe0/2+-SRB exhibited a well-developed surface pore structure. When the adsorption layer height was 200 mm, the influent flow rate was 5 × 10-5 m3/s, and the initial manganese ion concentration was 10 mg/L, the maximum dynamic adsorption capacities (qe) of Mn2+ for each dynamic column were 7.8430, 4.7627, and 8.7677 mg/g, respectively. Compared to dynamic columns 1# and 2#, dynamic column 3# showed the best performance in treating AMD, and the Thomas model effectively described the adsorption kinetics of Mn2+ by Fe0/2+-SRB(3#). Microstructural analysis indicated that chemical adsorption, ion exchange, dissimilation-reduction reaction, and surface complexation occurred between the various matrix materials in Fe0/2+-SRB(3#). Mn2+ was primarily removed in the form of metal sulfide (MnS), and Fe0/Fe2+ could promote the dissimilatory reduction of SO42- by SRB to form S2-. Fe0/2+-SRB(3#) was able to adapt to AMD with initial conditions of pH was 2~4, SO42- < 2500 mg/L, and Mn2+ < 20 mg/L. The research results provide new insights into the remediation of AMD, using a combined microbial-adsorption technology.

6.
Org Lett ; 26(36): 7632-7637, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39235108

RESUMEN

Penicillium daleae L3SO is a fungus isolated from the rhizospheric soil of the chloroplast-deficient plant Monotropa uniflora. A chemical study on the rice fermentation of this fungus led to the isolation and identification of two cage-like polyketides, penidaleodiolide A (1) and its biosynthetic-related congener penidaleodiolide B (2). The structures of 1 and 2 were determined by a combination of extensive spectroscopic analysis, biosynthetic consideration, chemical derivatization, and computational methods. Compound 1 harbors an unusual tricyclo[4.3.04,9]nonane scaffold, unprecedented in polyketide natural products. The hypothetical biosynthetic pathways for 1 and 2 were postulated and were supported by CRISPR/Cas9 genome editing results. Penidaleodiolide A (1) showed a significant inhibitory effect on the action potentials of murine hippocampal basket neurons and decreased the frequency of spontaneous excitatory postsynaptic currents in a concentration-dependent manner (the inhibition ratios were 0.30 ± 0.02 for 1 µM, 0.37 ± 0.03 for 10 µM, and 0.50 ± 0.07 for 20 µM) while being devoid of cytotoxicity against the nerve cells.


Asunto(s)
Penicillium , Policétidos , Policétidos/química , Policétidos/farmacología , Policétidos/aislamiento & purificación , Penicillium/química , Penicillium/metabolismo , Animales , Ratones , Estructura Molecular , Transmisión Sináptica/efectos de los fármacos , Microbiología del Suelo , Neuronas/efectos de los fármacos , Hipocampo/metabolismo
7.
Mol Cell Biochem ; 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39231894

RESUMEN

The degradation of proteasomes or lysosomes is emerging as a principal determinant of programmed death ligand 1 (PDL1) expression, which affects the efficacy of immunotherapy in various malignancies. Intracellular cholesterol plays a central role in maintaining the expression of membrane receptors; however, the specific effect of cholesterol on PDL1 expression in cancer cells remains poorly understood. Cholesterol starvation and stimulation were used to modulate the cellular cholesterol levels. Immunohistochemistry and western blotting were used to analyze the protein levels in the samples and cells. Quantitative real-time PCR, co-immunoprecipitation, and confocal co-localization assays were used for mechanistic investigation. A xenograft tumor model was constructed to verify these results in vivo. Our results showed that cholesterol suppressed the ubiquitination and degradation of PDL1 in hepatocellular carcinoma (HCC) cells. Further mechanistic studies revealed that the autocrine motility factor receptor (AMFR) is an E3 ligase that mediated the ubiquitination and degradation of PDL1, which was regulated by the cholesterol/p38 mitogenic activated protein kinase axis. Moreover, lowering cholesterol levels using statins improved the efficacy of programmed death 1 (PD1) inhibition in vivo. Our findings indicate that cholesterol serves as a signal to inhibit AMFR-mediated ubiquitination and degradation of PDL1 and suggest that lowering cholesterol by statins may be a promising combination strategy to improve the efficiency of PD1 inhibition in HCC.

8.
Mol Neurobiol ; 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39312067

RESUMEN

Exosomes, crucial extracellular vesicles, have emerged as potential biomarkers for neurological conditions, including schizophrenia (SCZ). However, the exploration of exosomal lipids in the context of SCZ remains scarce, necessitating in-depth investigation. Leveraging ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), this study aimed to characterize the lipidomic profile of serum exosomes from SCZ patients, assessing their potential as novel biomarkers for SCZ diagnosis through absolute quantitative lipidomics. Our comprehensive lipidomic analysis unveiled 39 serum exosomal lipids that were differentially expressed between SCZ patients (n = 20) and healthy controls (HC, n = 20). These findings revealed a profound dysregulation in lipid metabolism pathways, notably in sphingolipid metabolism, glycerophospholipid metabolism, and linoleic acid metabolism. Among these, seven exosomal lipids stood out for their diagnostic potential, exhibiting remarkable ability to differentiate SCZ patients from HCs with an unparalleled classification performance, evidenced by an area under the curve (AUC) of 0.94 (95% CI, 0.82-1.00). These lipids included specific ceramides and phosphoethanolamines, pointing to a distinct lipid metabolic fingerprint associated with SCZ. Furthermore, bioinformatic analyses reinforced the pivotal involvement of these lipids in SCZ-related lipid metabolic processes, suggesting their integral role in the disorder's pathophysiology. This study significantly advances our understanding of SCZ by pinpointing dysregulated exosomal lipid metabolism as a key factor in its pathology. The identified serum exosome-derived lipids emerge as compelling biomarkers for SCZ diagnosis, offering a promising avenue towards the development of objective and reliable diagnostic tools.

9.
Small ; : e2406497, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39285819

RESUMEN

Coal-based carbon material, characterized by abundant resources and low cost, has gained considerable interests as a promising anode candidate for sodium-ion batteries (SIBs). However, the coal-based carbon generally shows inferior Na-storage performance due to its highly-ordered microstructure with narrow interlayer spacing. Herein, a salt-assisted mechanical ball-milling strategy is proposed to disrupt the polycyclic aromatic hydrocarbon structure in anthracite molecules, thereby reducing the microcrystalline regularity of the derived carbon during following pyrolysis process. In addition, the induced C─O─C bonds during ball-milling process can alter the pyrolysis behavior of anthracite and restrain the formation of surface defects. Consequently, in contrast to pristine anthracite-based pyrolytic carbon, which exhibits a Na-storage capacity of 198.4 mAh g-1 with a low initial Coulombic efficiency (ICE) of 65.1%, the ball-milling modified carbon assisted by NaCl salt (NAC), with enhanced structural disordering and reduced surface defects, demonstrate significantly improved Na-storage capacity of 332.1 mAh g-1 and ICE value of 82.0%. The NAC electrode also realizes excellent cycle and rate performance, retaining a capacity of 196.0 mAh g-1 at 1 C after 1000 cycles. Furthermore, when coupled with NaNi1/3Fe1/3Mn1/3O2 cathode, the assembled Na-ion full cell deliveres an exceptional electrochemical performance, highlighting its promising prospect as high-performance anode for SIBs.

10.
Rev Sci Instrum ; 95(8)2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39212504

RESUMEN

The accelerating electrode of a four-dimensional transmission electron microscope electron gun is modeled. The general expression of the electric-field distribution is derived for any point on the axis in a cylindrical coordinate system, and equations for the shape parameters of the electrode plate are obtained. The accuracy of the field expression is determined for different electrode plate parameters, and the shape parameters of the electron gun electrode are further investigated. This work can provide a theoretical basis for the initial design of a transmission electron microscope electron gun and the retrofit design of a four-dimensional electron gun.

11.
BMC Ophthalmol ; 24(1): 323, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39103779

RESUMEN

INTRODUCTION: Early prediction and timely treatment are essential for minimizing the risk of visual loss or blindness of retinopathy of prematurity, emphasizing the importance of ROP screening in clinical routine. OBJECTIVE: To establish predictive models for ROP occurrence based on the risk factors using artificial neural network. METHODS: A cohort of 591 infants was recruited in this retrospective study. The association between ROP and perinatal factors was analyzed by univariate analysis and multivariable logistic regression. We developed predictive models for ROP screening using back propagation neural network, which was further optimized by applying genetic algorithm method. To assess the predictive performance of the models, the areas under the curve, sensitivity, specificity, negative predictive value, positive predictive value and accuracy were used to show the performances of the prediction models. RESULTS: ROP of any stage was found in 193 (32.7%) infants. Twelve risk factors of ROP were selected. Based on these factors, predictive models were built using BP neural network and genetic algorithm-back propagation (GA-BP) neural network. The areas under the curve for prediction models were 0.857, and 0.908 in test, respectively. CONCLUSIONS: We developed predictive models for ROP using artificial neural network. GA-BP neural network exhibited superior predictive ability for ROP when dealing with its non-linear clinical data.


Asunto(s)
Edad Gestacional , Redes Neurales de la Computación , Retinopatía de la Prematuridad , Humanos , Retinopatía de la Prematuridad/diagnóstico , Retinopatía de la Prematuridad/epidemiología , Estudios Retrospectivos , Recién Nacido , Femenino , Masculino , Factores de Riesgo , Valor Predictivo de las Pruebas , Curva ROC , Tamizaje Neonatal/métodos , Algoritmos
12.
Cancer Cell Int ; 24(1): 273, 2024 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-39097735

RESUMEN

BACKGROUND: The incidence of pancreatic cancer is increasing by years, and the 5-year survival rate is very low. Our team have revealed that Musashi2 (MSI2) could promote aggressive behaviors in pancreatic cancer by downregulating Numb and p53. MSI2 also facilitates EMT in pancreatic cancer induced by EGF through the ZEB1-ERK/MAPK signaling pathway. This study aims to further explore the molecular mechanisms of MSI2-regulated downstream pathways in pancreatic cancer. METHODS: In vitro and in vivo experiments were conducted to investigate the role and mechanism of MSI2 in promoting malignant behaviors of pancreatic cancer through regulation of NLK. RESULTS: Genes closely related to MSI2 were screened from the GEPIA and TCGA databases. We found that NLK showed the most significant changes in mRNA levels with consistent changes following MSI2 interference and overexpression. The high correlation between MSI2 and NLK was also observed at the protein level. Multivariate analysis revealed that both MSI2 and NLK were independent adverse indicators of survival in pancreatic cancer patients, as well as join together. In vitro, silencing or overexpressing NLK altered cell invasion and migration, by regulating EMT and the PI3K-AKT-mTOR pathway. Silencing MSI2 reduced protein expression in the EMT and PI3K-AKT-mTOR pathways, leading to decreased cell invasion and migration abilities, while these effects could be reversed by overexpression of NLK. In vivo, MSI2 silencing inhibited liver metastasis, which could be reversed by overexpressing NLK. Mechanistically, MSI2 directly binds to the translation regulatory region of NLK mRNA at positions 79-87 nt, enhancing its transcriptional activity and exerting post-transcriptional regulatory roles. The analysis of molecular docking showed the close relationship between MSI2 and NLK in pancreatic cancer patients. CONCLUSIONS: Our findings elucidate the regulatory mechanisms of the MSI2-NLK axis in modulating aggressive behaviors of pancreatic cancer cells, which providing new evidence for therapeutic strategies in pancreatic cancer.

13.
Nat Commun ; 15(1): 6703, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39112444

RESUMEN

Extreme myopia (EM), defined as a spherical equivalent (SE) ≤ -10.00 diopters (D), is one of the leading causes of sight impairment. Known EM-associated variants only explain limited risk and are inadequate for clinical decision-making. To discover risk genes, we performed a whole-exome sequencing (WES) on 449 EM individuals and 9606 controls. We find a significant excess of rare protein-truncating variants (PTVs) in EM cases, enriched in the retrograde vesicle-mediated transport pathway. Employing single-cell RNA-sequencing (scRNA-seq) and a single-cell polygenic burden score (scPBS), we pinpointed PI16 + /SFRP4+ fibroblasts as the most relevant cell type. We observed that KDELR3 is highly expressed in scleral fibroblast and involved in scleral extracellular matrix (ECM) organization. The zebrafish model revealed that kdelr3 downregulation leads to elongated ocular axial length and increased lens diameter. Together, our study provides insight into the genetics of EM in humans and highlights KDELR3's role in EM pathogenesis.


Asunto(s)
Secuenciación del Exoma , Mutación , Pez Cebra , Humanos , Animales , Pez Cebra/genética , Masculino , Femenino , Fibroblastos/metabolismo , Exoma/genética , Estudio de Asociación del Genoma Completo , Adulto , Miopía/genética , Miopía/metabolismo , Miopía/patología , Esclerótica/metabolismo , Esclerótica/patología , Matriz Extracelular/metabolismo , Matriz Extracelular/genética , Predisposición Genética a la Enfermedad , Análisis de la Célula Individual , Estudios de Casos y Controles , Niño , Adulto Joven
14.
Oncol Rep ; 52(4)2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39155875

RESUMEN

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that the western blot data shown for the MMP­9 experiment in Fig. 4 on p. 1493 were strikingly similar to the western blots shown for the total­Akt experiments in Fig. 6 on p. 1494. After having re­examined their original data files, the authors realized that Fig. 6 had been inadvertently assembled incorrectly. The revised version of Fig. 6, containing the correct data for the total­Akt experiments, is shown below. Note that the corrections made to this figure do not affect the overall conclusions reported in the paper. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [Oncology Reports 31: 1489­1497, 2014; DOI: 10.3892/or.2013.2961].

15.
Nat Commun ; 15(1): 7129, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39164230

RESUMEN

Alleviating water scarcity is at the core of Sustainable Development Goal 6. Yet the timing of water scarcity in its onset and possible relief in different regions of the world due to climate change and changing human population dynamics remains poorly investigated. Here we assess the timing of the first emergence of water scarcity (FirstWS) and disappearance of water scarcity (EndWS), by using ensembles of simulations with six Global Hydrological Models under two representative concentration pathways (i.e., RCP2.6, RCP6.0) combined with two shared socioeconomic pathways (i.e., SSP2, SSP3) for 1901-2090. Historically (1901-2020), FirstWS occurred predominantly in Asia (e.g., China and India) and Africa (e.g., East Africa); the peak time of emerging water scarcity began around the 1980s. Under all the four future RCPs-SSPs scenarios (2021-2090), FirstWS will likely occur mainly in some regions of Africa, for which the newly added area is double that in Asia. On the other hand, EndWS will mostly occur in China after 2050, primarily due to the projected declining population. We, therefore, call for specific attention and effort to adapt to the looming water scarcity in Africa.

16.
iScience ; 27(8): 110271, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39129827

RESUMEN

The strong resource constraints of edge-computing devices and the dynamic evolution of load characteristics put forward higher requirements for forecasting methods of active distribution networks. This paper proposes a lightweight adaptive ensemble learning method for local load forecasting and predictive control of active distribution networks based on edge computing in resource constrained scenarios. First, the adaptive sparse integration method is proposed to reduce the model scale. Then, the auto-encoder is introduced to downscale the model variables to further reduce computation time and storage overhead. An adaptive correction method is proposed to maintain the adaptability. Finally, a multi-timescale predictive control method for the edge side is established, which realizes the collaboration of local load forecasting and control. All cases can be deployed on an actual edge-computing device. Compared to other benchmark methods and the existing researches, the proposed method can minimize the model complexity without reducing the forecasting accuracy.

17.
J Hepatocell Carcinoma ; 11: 1311-1321, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38979082

RESUMEN

Purpose: There is limited research on whether Proton Pump Inhibitors (PPIs) will affect the efficacy of immune checkpoint inhibitors (ICIs) in treating hepatocellular carcinoma (HCC).This study aimed to determine whether PPIs affect the survival outcomes of patients with HBV-associated advanced HCC receiving combination therapy based on ICIs. Methods: We retrospectively analyzed patients with hepatitis B virus (HBV)-associated advanced HCC who underwent ICIs combination therapy from January 1, 2020, to December 30, 2022. Patients were stratified into PPI and non-PPI groups based on whether they received PPI treatment within 30 days before or after ICIs therapy. Patients' survival and the risk of PPI-associated mortality was assessed. Adverse events were also evaluated. Results: A total of 183 patients with HBV-associated HCC treated with ICI combination therapy were included. The median survival time (12.5 months vs 13.7 months, P = 0.285) and incidence of adverse events (P = 0.729) did not significantly differ between the PPI and non-PPI groups. Even after propensity score matching, the difference in median overall survival (OS) between the two groups was not significant (10.7 months vs 11.4 months; P = 0.596) and the patient's OS is not significantly related to the dosage of PPI application (P > 0.05).However, according to our subgroup analysis, among HCC patients with a serum HBV DNA concentration ≥ 200 IU/mL, the use of PPIs significantly increased the risk of mortality in patients receiving ICI combination therapy (P = 0.024). Conclusion: PPIs do not notably influence the survival prognosis of patients receiving ICI combination therapy for HBV-associated advanced HCC. However, among patients with high levels of HBV DNA, PPIs increase the risk of mortality. Therefore, antiviral therapy should be intensified in the patients with HBVDNA > 200 IU/mL. Additionally, PPIs do not impact the incidence of adverse reactions in these patients.

18.
Ophthalmic Res ; 67(1): 424-434, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38986459

RESUMEN

BACKGROUND: Presently, the global prevalence of myopia and high myopia reaches approximately 1.95 billion and 277 million individuals, respectively. Projections suggest that by 2050, the number of people with myopia may rise to 4.758 billion and those with high myopia to 938 million. In highly myopic eyes, the occurrence of MF is reported to be as high as 8-33%. SUMMARY: This review comprehensively addresses the classification, pathogenesis, natural progression, concomitant pathologies, and therapeutic strategies for macular foveoschisis in highly myopic patients. KEY MESSAGES: In recent years, macular foveoschisis has emerged as a prevalent complication in individuals with high myopia, primarily resulting from the combination of inward traction by vitreoretinal adhesions and outward traction exerted by posterior scleral staphyloma on the retina. While some maintain partial visual stability over an extended period, others may progress to macular holes or even retinal detachment. For highly myopic patients with macular foveoschisis, the mainstay procedures are vitrectomy, macular buckle, and posterior scleral reinforcement. However, there is controversy about whether to perform inner limiting membrane peeling and gas filling.


Asunto(s)
Miopía Degenerativa , Retinosquisis , Humanos , Retinosquisis/diagnóstico , Retinosquisis/etiología , Miopía Degenerativa/complicaciones , Miopía Degenerativa/diagnóstico , Miopía Degenerativa/fisiopatología , Tomografía de Coherencia Óptica/métodos , Agudeza Visual , Vitrectomía/métodos , Mácula Lútea/patología
19.
J Nanobiotechnology ; 22(1): 459, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39085911

RESUMEN

BACKGROUND: Sunitinib is a multikinase inhibitor used to treat patients with advanced renal cell carcinoma (RCC). However, sunitinib toxicity makes it a double-edged sword. Potent immune modulation by sunitinib extends to nuclear interactions. To address these issues, there is an urgent need for delivery vectors suitable for sunitinib treatment. METHODS: We developed PEGylated liposomes as delivery vectors to precisely target sunitinib (lipo-sunitinib) to RCC tumors. Further investigations, including RNA sequencing (RNA-seq), were performed to evaluate transcriptomic changes in these pathways. DiI/DiR-labeled lipo-sunitinib was used for the biodistribution analysis. Flow cytometry and immunofluorescence (IF) were used to examine immune modulation in orthotopic RCC models. RESULTS: The evaluation of results indicated that lipo-sunitinib precisely targeted the tumor site to induce autophagy and was readily taken up by RCC tumor cells. In addition, transcriptomic assays revealed that following lipo-sunitinib treatment, autophagy, antigen presentation, cytokine, and chemokine production pathways were upregulated, whereas the epithelial-mesenchymal transition (EMT) pathway was downregulated. In vivo data provided evidence supporting the inhibitory effect of lipo-sunitinib on RCC tumor progression and metastasis. Flow cytometry further demonstrated that liposunitinib increased the infiltration of effector T cells (Teffs) and conventional type 1 dendritic cells (cDC1s) into the tumor. Furthermore, systemic immune organs such as the tumor-draining lymph nodes, spleen, and bone marrow exhibited upregulated anticancer immunity following lipo-sunitinib treatment. CONCLUSION: Our findings demonstrated that lipo-sunitinib is distributed at the RCC tumor site, concurrently inducing potent autophagy, elevating antigen presentation, activating cytokine and chemokine production pathways, and downregulating EMT in RCC cells. This comprehensive approach significantly enhanced tumor inhibition and promoted anticancer immune modulation.


Asunto(s)
Autofagia , Carcinoma de Células Renales , Neoplasias Renales , Liposomas , Polietilenglicoles , Sunitinib , Carcinoma de Células Renales/tratamiento farmacológico , Sunitinib/farmacología , Autofagia/efectos de los fármacos , Animales , Liposomas/química , Neoplasias Renales/tratamiento farmacológico , Ratones , Línea Celular Tumoral , Polietilenglicoles/química , Humanos , Inmunomodulación/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/química , Distribución Tisular , Transición Epitelial-Mesenquimal/efectos de los fármacos , Femenino
20.
Oncoimmunology ; 13(1): 2381803, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39071160

RESUMEN

Tumor-derived exosomes bind to organ resident cells, activating S100 molecules during the remodeling of the local immune microenvironment. However, little is known regarding how organ resident cell S100A10 mediates cancer metastatic progression. Here, we provided evidence that S100A10 plays an important role in regulating the lung immune microenvironment and cancer metastasis. S100A10-deficient mice reduced cancer metastasis in the lung. Furthermore, the activation of S100A10 within lung fibroblasts via tumor-derived exosomes increased the expression of CXCL1 and CXCL8 chemokines, accompanied by the myeloid-derived suppressor cells (MDSCs) recruitment. S100A10 inhibitors such as 1-Substituted-4-Aroyl-3-hydroxy-5-Phenyl-1 H-5-pyrrol-2(5 H)-ones inhibit lung metastasis in vivo. Our findings highlight the crucial role of S100A10 in driving MDSC recruitment in order to remodel the lung immune microenvironment and provide potential therapeutic targets to block cancer metastasis to the lung.


Asunto(s)
Neoplasias Pulmonares , Células Supresoras de Origen Mieloide , Proteínas S100 , Microambiente Tumoral , Animales , Células Supresoras de Origen Mieloide/metabolismo , Células Supresoras de Origen Mieloide/inmunología , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Ratones , Microambiente Tumoral/inmunología , Proteínas S100/metabolismo , Proteínas S100/genética , Ratones Endogámicos C57BL , Línea Celular Tumoral , Humanos , Ratones Noqueados , Exosomas/metabolismo
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