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1.
Magn Reson Med ; 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39344297

RESUMEN

PURPOSE: This study aims to show the viability of conducting three-dimensional (3D) myocardial perfusion quantification covering the entire heart using both GRE and bSSFP sequences with hyperpolarized HP001. METHODS: A GRE sequence and a bSSFP sequence, both with a stack-of-spirals readout, were designed and applied to three pigs. The images were reconstructed using 13 $$ {}^{13} $$ C coil sensitivity maps measured in a phantom experiment. Perfusion was quantified using a constrained decomposition method, and the estimated rest/stress perfusion values from 13 $$ {}^{13} $$ C GRE/bSSFP and Dynamic contrast-enhanced MRI (DCE-MRI) were individually analyzed through histograms and the mean perfusion values were compared with reference values obtained from PET( 15 $$ {}^{15} $$ O-water). The Myocardial Perfusion Reserve Index (MPRI) was estimated for 13 $$ {}^{13} $$ C GRE/bSSFP and DCE-MRI and compared with the reference values. RESULTS: Perfusion values, estimated by both DCE and 13 $$ {}^{13} $$ C MRI, were found to be lower than reference values. However, DCE-MRI's estimated perfusion values were closer to the reference values than those obtained from 13 $$ {}^{13} $$ C MRI. In the case of MPRI estimation, the 13 $$ {}^{13} $$ C estimated MPRI values (GRE/bSSFP: 2.3/2.0) more closely align with the literature value (around 3) than the DCE estimated MPRI value (1.6). CONCLUSION: This study demonstrated the feasibility of 3D whole-heart myocardial perfusion quantification using hyperpolarized HP001 with both GRE and bSSFP sequences. The 13 $$ {}^{13} $$ C perfusion measurements underestimated perfusion values compared to the 15 $$ {}^{15} $$ O PET literature value, while the 13 $$ {}^{13} $$ C estimated MPRI value aligned better with the literature. This preliminary result indicates 13 $$ {}^{13} $$ C imaging may more accurately estimate MPRI values compared to DCE-MRI.

2.
Cancer Cell Int ; 24(1): 167, 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38734676

RESUMEN

BACKGROUND: Accumulating evidences indicate that the specific alternative splicing (AS) events are linked to the occurrence and prognosis of gastric cancer (GC). Nevertheless, the impact of AS is still unclear and needed to further elucidation. METHODS: The expression profile of GC and normal samples were downloaded from TCGA. AS events were achieved from SpliceSeq database. Cox regression together with LASSO analysis were employed to identify survival-associated AS events (SASEs) and calculate risk scores. PPI and pathway enrichment analysis were implemented to determine the function and pathways of these genes. Kaplan-Meier (K-M) analysis and Receiver Operating Characteristic Curves were used to evaluate the clinical significance of genes of SASEs. Q-PCR were applied to validate the hub genes on the survival prognosis in 47 GC samples. Drug sensitivity and immune cell infiltration analysis were conducted. RESULTS: In total, 48 140 AS events in 10 610 genes from 361 GC and 31 normal samples were analyzed. Through univariate Cox regression, 855 SASEs in 763 genes were screened out. Further, these SASEs were analyzed by PPI and 17 hub genes were identified. Meanwhile, using Lasso and multivariate Cox regression analysis, 135 SASEs in 132 genes related to 7 AS forms were further screened and a GC prognostic model was constructed. K-M curves indicates that high-risk group has poorer prognosis. And the nomogram analysis on the basis of the multivariate Cox analysis was disclosed the interrelationships between 7 AS forms and clinical parameters in the model. Five key genes were then screened out by PPI analysis and Differential Expression Gene analysis based on TCGA and Combined-dataset, namely STAT3, RAD51B, SOCS2, POLE2 and TSR1. The expression levels of AS in STAT3, RAD51B, SOCS2, POLE2 and TSR1 were all significantly correlated with survival by qPCR verification. Nineteen drugs were sensitized to high-risk patients and eight immune cells showed significantly different infiltration between the STAD and normal groups. CONCLUSIONS: In this research, the prognostic model constructed by SASEs can be applied to predict the prognosis of GC patients and the selected key genes are expected to become new biomarkers and therapeutical targets for GC treatment.

3.
Chemistry ; 29(13): e202203220, 2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36458818

RESUMEN

The design of efficient and stable oxygen evolution reaction (OER) catalysts based on noble-metal-free materials is crucial for energy conversion and storage. In this work, it was demonstrated how polyoxometalate (POM)-doped ZIF-67 can be converted into a stable oxygen evolution electrocatalyst by chemical etching, cation exchange, and thermal annealing steps. Characterization by X-ray photoelectron spectroscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy and Raman spectroscopy indicate that POM-doped ZIF-67 derived carbon-supported metal oxides were synthesized. The resulting composite shows structural and compositional advantages which lead to low overpotential (306 mV at j=10 mA ⋅ cm-2 ) and long-term stability under harsh OER conditions (1.0 M aqueous KOH).

4.
J Org Chem ; 88(14): 10257-10265, 2023 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-37400425

RESUMEN

Different chemoselectivities of phenols and thiophenols were observed in a Tf2O-promoted C3 functionalization of simple anthranils. The reaction of phenols and anthranils gives 3-aryl anthranils via a C-C bond formation, whereas thiophenols afford 3-thio anthranils through a C-S bond formation. Both reactions have a broad substrate scope and tolerate a wide range of functional groups, affording the corresponding products with specific chemoselectivity.

5.
Gastric Cancer ; 26(4): 565-579, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37062785

RESUMEN

BACKGROUND: Gastric cancer (GC) is a cancer of the gastrointestinal tract that is highly malignant and has poor prognosis. Circular RNAs are a class of nonclassical RNA molecules that have been determined to be involved in GC malignancy in various ways. However, the underlying function and mechanism of circTDRD3 in gastric cancer remain largely unknown. METHODS: We analyzed circTDRD3 expression in databases and verified the findings in GC cell lines and tissue specimens. A series of functional gene overexpression and knockdown assays in vivo and in vitro were carried out to investigate the role of circTDRD3 in proliferation and metastasis. Here, we revealed the role of the miR-891b/ITGA2 axis by analyzing bioinformatics datasets. Furthermore, we performed dual-luciferase, fluorescence in situ hybridization, RNA pull-down, and functional rescue experiments to examine the relationships between circTDRD3 and its interacting molecules. Western blot confirmed the positive regulatory role of circTDRD3 in the AKT signaling pathway. A promoting effect of ATF4 on circTDRD3 was determined through chromatin immunoprecipitation. RESULTS: CircTDRD3 was significantly overexpressed in GC tissues compared with adjacent benign tissue, and its expression level was positively correlated with tumor volume and lymph node metastasis. CircTDRD3 promoted GC cell proliferation and migration in vitro and in vivo. Mechanistically, circTDRD3 exerted a tumor-promoting effect by regulating the miR-891b/ITGA2 axis and AKT signaling pathway in a positive feedback manner mediated by the transcription factor ATF4. CONCLUSIONS: ATF4-mediated circTDRD3 overexpression modulates the proliferation and metastasis of GC cells through the miR-891b/ITGA2 axis in a positive feedback manner.


Asunto(s)
MicroARNs , Neoplasias Gástricas , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Neoplasias Gástricas/patología , Hibridación Fluorescente in Situ , Transducción de Señal , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral , Factor de Transcripción Activador 4/genética , Factor de Transcripción Activador 4/metabolismo
6.
Angew Chem Int Ed Engl ; 62(50): e202314999, 2023 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-37889729

RESUMEN

The activation of molecular hydrogen is a key process in catalysis. Here, we demonstrate how polyoxometalate (POM)-based heterogeneous compounds functionalized with Platinum particles activate H2 by synergism between a hydrogen spillover mechanism and electron-proton transfer by the POM. This interplay facilitates the selective catalytic reduction of olefins and nitroarenes with high functional group tolerance. A family of polyoxotungstates covalently functionalized with boronic acids is reported. In the solid-state, the compounds are held together by non-covalent interactions (π-π stacking and hydrogen bonding). The resulting heterogeneous nanoscale particles form stable colloidal dispersions in acetonitrile and can be surface-functionalized with platinum nanoparticles by in situ photoreduction. The resulting materials show excellent catalytic activity in hydrogenation of olefins and nitrobenzene derivatives under mild conditions (1 bar H2 and room temperature).

7.
Opt Express ; 30(12): 21349-21361, 2022 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-36224856

RESUMEN

Versatile applications have driven a desire for dual-band detection that enables seeing objects in multiple wavebands through a single photodetector. In this paper, a concept of using graphene/p-GaN Schottky heterojunction on top of a regular AlGaN-based p-i-n mesa photodiode is reported for achieving solar-/visible-blind dual-band (275 nm and 365 nm) ultraviolet photodetector with high performance. The highly transparent graphene in the front side and the polished sapphire substrate at the back side allows both top illumination and back illumination for the dual band detection. A system limit dark current of 1×10-9 A/cm2 at a negative bias voltage up to -10 V has been achieved, while the maximum detectivity obtained from the detection wavebands of interests at 275 nm and 365 nm are ∼ 9.0 ×1012 cm·Hz1/2/W at -7.5 V and ∼8.0 × 1011 cm·Hz1/2/W at +10 V, respectively. Interestingly, this new type of photodetector is dual-functional, capable of working as either photodiode or photoconductor, when switched by simply adjusting the regimes of bias voltage applied on the devices. By selecting proper bias, the device operation mode would switch between a high-speed photodiode and a high-gain photoconductor. The device exhibits a minimum rise time of ∼210 µs when working as a photodiode and a maximum responsivity of 300 A/W at 6 µW/cm2 when working as a photoconductor. This dual band and multi-functional design would greatly extend the utility of detectors based on nitrides.

8.
J Biol Chem ; 291(35): 18252-62, 2016 08 26.
Artículo en Inglés | MEDLINE | ID: mdl-27387505

RESUMEN

The endoplasmic reticulum (ER) network comprises sheets and tubules that are connected by dynamic three-way junctions. Lunapark (Lnp) localizes to and stabilizes ER three-way junctions by antagonizing the small GTPase Atlastin, but how Lnp shapes the ER network is unclear. Here, we used an affinity purification approach and mass spectrometry to identify Lnp as an interacting partner of the ER protein quality control ubiquitin ligase gp78. Accordingly, Lnp purified from mammalian cells has a ubiquitin ligase activity in vitro Intriguingly, biochemical analyses show that this activity can be attributed not only to associated ubiquitin ligase, but also to an intrinsic ubiquitin ligase activity borne by Lnp itself. This activity is contained in the N-terminal 45 amino acids of Lnp although this segment does not share homology to any known ubiquitin ligase motifs. Despite its interaction with gp78, Lnp does not seem to have a broad function in degradation of misfolded ER proteins. On the other hand, the N-terminal ubiquitin ligase-bearing motif is required for the ER three-way junction localization of Lnp. Our study identifies a new type of ubiquitin ligase and reveals a potential link between ubiquitin and ER morphology regulation.


Asunto(s)
Retículo Endoplásmico/metabolismo , Proteínas de Homeodominio/metabolismo , Receptores del Factor Autocrino de Motilidad/metabolismo , Secuencias de Aminoácidos , Animales , Células COS , Chlorocebus aethiops , Retículo Endoplásmico/genética , Proteínas de Unión al GTP/genética , Proteínas de Unión al GTP/metabolismo , Células HeLa , Proteínas de Homeodominio/genética , Humanos , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Transporte de Proteínas , Receptores del Factor Autocrino de Motilidad/genética
9.
Genetica ; 145(1): 1-7, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27858207

RESUMEN

The Dlk1-Dio3 imprinted domain is located on the cattle chromosome 21 and contains three paternally expressed protein-coding genes and a number of maternally expressed short or long noncoding RNA genes. We have previously obtained two maternally expressed long noncoding RNA genes, Meg8 and Meg9, from the cattle. In this study, we identified a novel noncoding RNA located between Meg8 and Meg9 known as LINC24061 according to the GENCODE annotated bibliography. Two alternatively spliced transcripts (LINC24061-v1 and LINC24061-v2) were obtained using RT-PCR and RACE, and the expression pattern of LINC24061-v1 and LINC24061-v2 was shown to be tissue-specific. The LINC24061-v1 splice variant was expressed in only three types of tissues: heart, kidney and muscle; in contrast, LINC24061-v2 was expressed in all eight tissues examined, including heart, liver, spleen, lung, kidney, skeletal muscle, subcutaneous fat, and brain of adult cattle. The allele-specific expression of LINC24061 was identified based on a single nucleotide polymorphism (SNP) in exon 2 of LINC24061. The results showed that LINC24061 exhibited monoallelic expression in all the examined cattle tissues.


Asunto(s)
Cromosomas , Impresión Genómica , ARN Largo no Codificante , Alelos , Empalme Alternativo , Animales , Bovinos , Clonación Molecular , Expresión Génica , Perfilación de la Expresión Génica , Orden Génico , Sitios Genéticos , Genotipo , Polimorfismo de Nucleótido Simple
10.
Apoptosis ; 21(1): 69-84, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26456506

RESUMEN

Pulmonary arterial hypertension (PAH) is a life-threatening disorder that ultimately causes heart failure. While the underlying causes of this condition are not well understood, previous studies suggest that the anti-apoptotic nature of pulmonary microvascular endothelial cells (PMVECs) in hypoxic environments contributes to PAH pathogenesis. In this study, we focus on the contribution of Bcl-2 and hypoxia response element (HRE) to apoptosis-resistant endothelial cells and investigate the mechanism. PMVECs obtained from either normal rats or apoptosis-resistant PMVECs obtained from PAH rats were transduced with recombinant lentiviral vectors carrying either Bcl-2-shRNA or HRE combined Bcl-2-shRNA, and then cultured these cells for 24 h under hypoxic (5% O2) or normoxic (21% O2) conditions. In normal PMVECs, Bcl-2-shRNA or HRE combined with Bcl-2-shRNA transduction successfully decreased Bcl-2 expression, while increasing apoptosis as well as caspase-3 and P53 expression in a normoxic environment. In a hypoxic environment, the effects of Bcl-2-shRNA treatment on cell apoptosis, and on Bcl-2, caspase-3, P53 expression were significantly suppressed. Conversely, HRE activation combined with Bcl-2-shRNA transduction markedly enhanced cell apoptosis and upregulated caspase-3 and P53 expression, while decreasing Bcl-2 expression. Furthermore, in apoptosis-resistant PMVECs, HRE-mediated Bcl-2 silencing effectively enhanced cell apoptosis and caspase-3 activity. The apoptosis rate was significantly depressed when Lv-HRE-Bcl-2-shRNA was combined with Lv-P53-shRNA or Lv-caspase3-shRNA transduction in a hypoxic environment. These results suggest that HRE-mediated Bcl-2 inhibition can effectively attenuate hypoxia-induced apoptosis resistance in PMVECs by downregulating Bcl-2 expression and upregulating caspase-3 and P53 expression. This study therefore reveals critical insight into potential therapeutic targets for treating PAH.


Asunto(s)
Apoptosis/genética , Células Endoteliales/metabolismo , Hipertensión/genética , Proteínas Proto-Oncogénicas c-bcl-2/genética , Elementos de Respuesta , Animales , Caspasa 3/genética , Caspasa 3/metabolismo , Hipoxia de la Célula , Células Endoteliales/patología , Regulación de la Expresión Génica , Vectores Genéticos/química , Vectores Genéticos/metabolismo , Hipertensión/inducido químicamente , Hipertensión/metabolismo , Hipertensión/patología , Lentivirus/genética , Lentivirus/metabolismo , Pulmón/irrigación sanguínea , Pulmón/patología , Masculino , Monocrotalina , Cultivo Primario de Células , Proteínas Proto-Oncogénicas c-bcl-2/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Arteria Pulmonar/metabolismo , Arteria Pulmonar/patología , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal , Transducción Genética , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo
11.
RSC Adv ; 14(24): 16912-16920, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38799222

RESUMEN

In this study, polypropylene/halloysite nanotube (PP/HNT) composite separators were prepared by coating HNTs treated with hydrochloric acid (HCl) of different concentrations on both sides of a PP separator. The effect of HNTs treated with hydrochloric acid (HCl) of different concentrations on the properties of PP/HNT composite separators was investigated. The results indicate that the PP/HNT composite separator exhibits higher electrolyte uptake and wettability than a commercial PP separator, resulting in a better electrochemical performance in Li/LiFePO4 cells. In particular, the PP/HNTs-1.2 M composite separator with HNTs treated with 1.2 M HCl exhibits the highest electrolyte uptake (384%) and ionic conductivity (1.03 mS cm-1). The cells assembled with a PP/HNTs-1.2 M composite separator deliver discharge capacities of 166 mA h g-1 (0.5 C) and 131 mA h g-1 (3 C) with attractive cycling performance (87.6% capacity retention after 100 cycles). HNTs treated with HCl of appropriate concentrations can significantly improve the properties of PP/HNT composite separators for application in lithium-ion batteries.

12.
Spectrochim Acta A Mol Biomol Spectrosc ; 317: 124449, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-38754206

RESUMEN

To explore the intrinsic mechanism of pure organic room temperature and clustering-induced phosphorescence and investigate mechanochromism and structural-function relationships, here, 4-(2-(9H-carbazol-9-yl)phenyl)-2-amino-6-methoxypyridine-3,5-dicarbonitrile (Lo-CzAD), 4-(3-(9H-carbazol-9-yl)phenyl)-2-amino-6-methoxypyridine-3,5-dicarbonitrile (Lm-CzAD), and 4-(4-(9H-carbazol-9-yl)phenyl)-2-amino-6-methoxypyridine-3,5-dicarbonitrile (Lp-CzAD) were designed and synthesized by choosing self-made carbazole and 3, 5-dicyanopyridine (DCP) unit as electron acceptor and electron donor in sequence. Compared with crystals Lm-CzAD and Lp-CzAD, crystal Lo-CzAD shows better room temperature phosphorescence (RTP) performance, with RTP lifetimes of 187.16 ms, as well as afterglows 1s, which are attributed to twisted carbazole unit and donor-acceptor (D-A) molecular conformation, big crystal density and spin orbit coupling constant ξ (S1 â†’ T1 and S1 â†’ T2), as well as intermolecular H type stacking and small ξ (S0 â†’ T1). By choosing urea and PPh3 as host materials and tuning doping ratio, four doping systems were successfully constructed, significantly improving RTP performance of Lo-CzAD and Lp-CzAD, as well as showing different fluorescence and RTP. The lifetimes and afterglows of pure organic Urea/Lo-CzAD and Urea/Lp-CzAD systems are up to 478.42 ms, 5 s, 261.66 ms and 4.5 s in turn. Moreover, Lo-CzAD and Lp-CzAD show time-dependent RTP in doping systems due to monomer and aggregate dispersion, as well as clustering-induced phosphorescence. Based on the different luminescent properties, multiple information encryptions were successfully constructed.

13.
Front Plant Sci ; 15: 1441613, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39315367

RESUMEN

Introduction: Wetlands are ecosystems that have a significant impact on ecological services and are essential for the environment. With the impacts of rapid population growth, wetland reclamation, urbanization, and land use change, wetlands have undergo severe degradation or loss. However, the response of soil fungal communities to wetland degradation remains unknown. It is crucial to comprehend how the diversity and population dynamics of soil fungi respond to varying levels of degradation and ecological progression in the wetlands of the Songnen Plain. Methods: In this study, high- throughput sequencing technology to analyze the variety and abundance of soil fungi in the undegraded (UD), light degraded (LD), moderate degraded (MD), and severe degraded (SD) conditions in the Halahai Nature Reserve of Songnen Plain. This study also explored how these fungi are related to the soil's physicochemical properties in wetlands at various degradation levels. Results: The findings indicated that Basidiomycota and Ascomycota were the primary phyla in the Songnen Plain, with Ascomycota increasing and Basidiomycota decreasing as wetland degradation progressed. Significant differences were observed in soil organic carbon (SOC), total nitrogen (TN),and soil total potassium (TK) among the succession degradation stages. With the deterioration of the wetland, there was a pattern of the Shannon and Chao1 indices increasing and then decreasing. Non-metric Multidimensional Scaling (NMDS) analysis indicated that the fungal community structures of UD and LD were quite similar, whereas MD and SD exhibited more distinct differences in their fungal community compositions. Redundancy analysis (RDA) results indicated that Soil Water content (SWC) and total nitrogen (TN) were the primary environmental factors influencing the dominant fungal phylum. According to the FUNGuild prediction, Ectomycorrhizal and plant pathogens gradually declining with wetland degradation. Discussion: In general, our findings can offer theoretical support develop effective solutions for the preservation and rehabilitation of damaged wetlands.

14.
Carbohydr Polym ; 335: 121920, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38616070

RESUMEN

Natural polymer-based hydrogels have been wildly used in electronic skin, health monitoring and human motion sensing. However, the construction of hydrogel with excellent mechanical strength and electrical conductivity totally using natural polymers still faces many challenges. In this paper, gelatin and oxidized sodium carboxymethylcellulose were used to synthesize a double-network hydrogel through the dynamic Schiff base bonds. Then, the mechanical strength of the hydrogel was further enhanced by immersing it in an ammonium sulfate solution based on the Hofmeister effect between gelatin and salt. Finally, the gelatin/oxidized sodium carboxymethylcellulose hydrogel exhibited high tensile properties (614 %), tensile fracture strength (2.6 MPa), excellent compressive fracture strength (64 MPa), and compressive toughness (4.28 MJ/m3). Also, the electrical conductivity reached 3.94 S/m. The hydrogel after salt soaked was fabricated as strain sensors, which could accurately monitor the movement of many joints in the human body, such as fingers, wrists, elbows, neck, and throat. Therefore, the designed hydrogel fully originated from natural polymers and has great application potential in motion detection and information recording.

15.
Adv Sci (Weinh) ; 11(39): e2405187, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39159133

RESUMEN

Defect engineering is a key chemical tool to modulate the electronic structure and reactivity of nanostructured catalysts. Here, it is reported how targeted introduction of defect sites in a 2D palladium metallene nanostructure results in a highly active catalyst for the alkaline oxygen reduction reaction (ORR). A defect-rich WOx and MoOx modified Pd metallene (denoted: D-Pd M) is synthesized by a facile and scalable approach. Detailed structural analyses reveal the presence of three distinct atomic-level defects, that are pores, concave surfaces, and surface-anchored individual WOx and MoOx sites. Mechanistic studies reveal that these defects result in excellent catalytic ORR activity (half-wave potential 0.93 V vs. RHE, mass activity 1.3 A mgPd-1 at 0.9 V vs. RHE), outperforming the commercial references Pt/C and Pd/C by factors of ≈7 and ≈4, respectively. The practical usage of the compound is demonstrated by integration into a custom-built Zn-air battery. At low D-Pd M loading (26 µgPd cm-2), the system achieves high specific capacity (809 mAh gZn -1) and shows excellent discharge potential stability. This study therefore provides a blueprint for the molecular design of defect sites in 2D metallene nanostructures for advanced energy technology applications.

16.
Biochem Pharmacol ; 222: 116120, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38461905

RESUMEN

The role of the Immunoglobulin Superfamily (IgSF) as adhesion molecules in orchestrating inflammation is pivotal, yet its specific involvement in gastric cancer (GC) remains unknown. We analyzed IgSF components and discerned conspicuously elevated VCAM1 expression in GC, correlating with a poor prognosis. Remarkably, VCAM1 enhances GC cell proliferation and migration by activating AKT-mTOR signaling. Moreover, lactate in the tumor microenvironment (TME) promotes dynamic lactylation of H3K18 (H3K18la), leading to transcriptional activation of VCAM1 in GC cells. Furthermore, VCAM1 actively mediates intercellular communication in the TME. AKT-mTOR-mediated CXCL1 expression is increased by VCAM1, facilitating the recruitment of human GC-derived mesenchymal stem cells (hGC-MSCs), thereby fostering immunesuppression and accelerating cancer progression. In summary, H3K18 lactylation upregulated VCAM1 transcription, which activated AKT-mTOR signaling, and promoted tumor cell proliferation, EMT Transition and tumor metastasis. VCAM1 upregulated CXCL1 expression by AKT-mTOR pathway, so as to facilitate hGC-MSCs and M2 macrophage recruitment and infiltration. These findings provide novel therapeutic targets for GC.


Asunto(s)
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Movimiento Celular , Transducción de Señal , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Línea Celular Tumoral , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Transición Epitelial-Mesenquimal , Microambiente Tumoral , Quimiocina CXCL1/metabolismo
17.
Int Immunopharmacol ; 132: 111998, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38593510

RESUMEN

BACKGROUND: Given the intricate molecular complexities and heterogeneity inherent in T-cell immunotherapy of gastric cancer (GC), elucidative T-cell-related biomarkers were imperative needed for facilitating the prediction of GC patient prognosis and identify potential synergistic therapeutic targets. METHODS: We conducted COX regression analysis in TISIDB, TCGA-STAD, and GEO databases to identify 19 GC T-cell-mediated sensitivity tumor killing (TTK) genes (key GCTTKs). Based on key GCTTKs, we constructed two TTK patterns and analyzed their metabolic pathways, mutation features, clinical data distribution, immune cell infiltration, and prognosis. LASSO regression was performed to develop a T-cell-mediated GC Prognosis (TGCP) model. We validated the TGCP model in GC patients. TAP1 was further selected for investigation of its biological functions and molecular mechanisms. We assessed the potential of TAP1 as a promising therapeutic target for GC using Patient-derived organoids (PDOs)-derived xenografts (PDOXs) models of GC. RESULTS: The TTK patterns display notable disparities. The TGCP model showcases its proficiency in predicting immune response efficacy, effectively distinguishes immunotherapy difference GC patients. Our findings find further confirmation in PDOX models, affirming TAP1 can enhance immunotherapy facilitated by PDL1 inhibitors. Furthermore, Oxaliplatin, by promoting TAP1 expression, augments PDL1 expression, thereby enhancing the efficacy of immunotherapy. CONCLUSIONS: We constructed a TGCP model, which demonstrates satisfactory predictive accuracy. Out of 9 prognostic genes, TAP1 was validated as a synergistic target for Oxaliplatin and PDL1 inhibitors, offering a genetic-level explanation for the synergy observed in GC treatment involving Oxaliplatin in combination with PDL1 inhibitors.


Asunto(s)
Transportador de Casetes de Unión a ATP, Subfamilia B, Miembro 2 , Inmunoterapia , Oxaliplatino , Neoplasias Gástricas , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/terapia , Neoplasias Gástricas/genética , Humanos , Animales , Oxaliplatino/farmacología , Oxaliplatino/uso terapéutico , Inmunoterapia/métodos , Transportador de Casetes de Unión a ATP, Subfamilia B, Miembro 2/genética , Ratones , Linfocitos T/inmunología , Línea Celular Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto , Sinergismo Farmacológico , Pronóstico
18.
Tomography ; 10(7): 1113-1122, 2024 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-39058056

RESUMEN

Purpose: Water freely diffuses across cell membranes, making it suitable for measuring absolute tissue perfusion. In this study, we introduce an imaging method for conducting coronary artery angiography and quantifying myocardial perfusion across the entire heart using hyperpolarized water. Methods:1H was hyperpolarized using dissolution dynamic nuclear polarization (dDNP) with UV-generated radicals. Submillimeter resolution coronary artery images were acquired as 2D projections using a spoiled GRE (SPGRE) sequence gated on diastole. Dynamic perfusion images were obtained with a multi-slice SPGRE with diastole gating, covering the entire heart. Perfusion values were analyzed through histograms, and the most frequent estimated perfusion value (the mode of the distribution), was compared with the average values for 15O water PET from the literature. Results: A liquid state polarization of 10% at the time of the injection and a 30 s T1 in D2O TRIS buffer were measured. Both coronary artery and dynamic perfusion images exhibited good quality. The main and small coronary artery branches were well resolved. The most frequent estimated perfusion value is around 0.6 mL/g/min, which is lower than the average values obtained from the literature for 15O-water PET (around 1.1 and 1.5 mL/g/min). Conclusions: The study successfully demonstrated the feasibility of achieving high-resolution, motion-free coronary artery angiography and 3D whole-heart quantitative myocardial perfusion using hyperpolarized water.


Asunto(s)
Angiografía Coronaria , Vasos Coronarios , Agua , Humanos , Angiografía Coronaria/métodos , Vasos Coronarios/diagnóstico por imagen , Imagen de Perfusión Miocárdica/métodos , Masculino , Radioisótopos de Oxígeno , Corazón/diagnóstico por imagen , Femenino , Circulación Coronaria/fisiología
19.
RSC Adv ; 13(10): 6606-6618, 2023 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-36845586

RESUMEN

Hierarchical hollow tubular porous carbons have been widely used in applications of supercapacitors, batteries, CO2 capture and catalysis due to their hollow tubular morphology, large aspect ratio, abundant pore structure and superior conductivity. Herein, hierarchical hollow tubular fibrous brucite-templated carbons (AHTFBCs) were prepared using natural mineral fiber brucite as the template and KOH as the chemical activator. The effects of different KOH additions on the pore structure and capacitive performance of AHTFBCs were systematically studied. The specific surface area and micropore content of AHTFBCs after KOH activation were higher than those of HTFBC. The specific surface area of the HTFBC is 400 m2 g-1, while the activated AHTFBC5 has a specific surface area of up to 625 m2 g-1. In particular, compared with HTFBC (6.1%), a series of AHTFBCs (22.1% for AHTFBC2, 23.9% for AHTFBC3, 26.8% for AHTFBC4 and 22.9% for AHTFBC5) with significantly increased micropore content were prepared by controlling the amount of KOH added. The AHTFBC4 electrode displays a high capacitance of 197 F g-1 at 1 A g-1 and the capacitance retention of 100% after 10 000 cycles at 5 A g-1 in the three-electrode system. And an AHTFBC4//AHTFBC4 symmetric supercapacitor exhibits the capacitance of 109 F g-1 at 1 A g-1 in 6 M KOH and an energy density of 5.8 W h kg-1 at 199.0 W kg-1 in 1 M Na2SO4 electrolyte. In addition, the capacity retention of AHTFBC4 in the symmetric supercapacitor was maintained at 92% after 5000 cycles in both 6 M KOH and 1 M Na2SO4 electrolytes.

20.
Chem Commun (Camb) ; 59(14): 1889-1906, 2023 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-36661267

RESUMEN

Recent progress on catalytic nitrene transfer reactions with hydroxylamine derivatives as prevalent precursors is summarized in this highlight. The salient features of these N-O derived nitrene transfer reagents are that they are readily available, bench-stable, and can be facilely activated by a range of transition metal-catalysts under mild conditions. The application of these reagents in transition metal-catalysis has led to many new amidation or amination reactions, such as C-H insertions and aziridination of olefins. These reagents have also been applied in difunctionalisation of unsaturated bonds, dearomative amination of indoles, and formation of N-X bonds. Moreover, the recent achievements in photocatalysis and enzyme catalysis further emphasize the importance of these appealing reagents. This highlight provides an overview of these reactions reported in recent years. Challenges and potential opportunities for future developments are also discussed.

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