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1.
Proc Natl Acad Sci U S A ; 120(14): e2218261120, 2023 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-36972459

RESUMEN

The ability to construct metal single-atom catalysts (SACs) asymmetrically coordinated with organic heteroatoms represents an important endeavor toward developing high-performance catalysts over symmetrically coordinated counterparts. Moreover, it is of key importance in creating supporting matrix with porous architecture for situating SACs as it greatly impacts the mass diffusion and transport of electrolyte. Herein, we report the crafting of Fe single atoms with asymmetrically coordinated nitrogen (N) and phosphorus (P) atoms scaffolded by rationally designed mesoporous carbon nanospheres (MCNs) with spoke-like nanochannels for boosting ring-opening reaction of epoxide to produce an array of pharmacologically important ß-amino alcohols. Notably, interfacial defects in MCN derived from the use of sacrificial template create abundant unpaired electrons, thereby stably anchoring N and P atoms and in turn Fe atoms on MCN. Importantly, the introduction of P atom promotes the symmetry-breaking of common four N-coordinated Fe sites, resulting in the Fe-N3P sites on MCN (denoted Fe-N3P-MCN) with an asymmetric electronic configuration and thus superior catalytic capability. As such, the Fe-N3P-MCN catalysts manifest a high catalytic activity for ring-opening reaction of epoxide (97% yield) over the Fe-N3P docked on nonporous carbon surface (91%) as well as the sole Fe-N4 SACs grounded on the same MCN support (89%). Density functional theory calculations reveal that Fe-N3P SAC lowers the activation barrier for the C-O bond cleavage and the C-N bond formation, thus accelerating the ring-opening of epoxide. Our study provides fundamental and practical insights into developing advanced catalysts in a simple and controllable manner for multistep organic reactions.

2.
Proc Natl Acad Sci U S A ; 120(26): e2303262120, 2023 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-37339215

RESUMEN

Graphene nanoribbons (GNRs) are widely recognized as intriguing building blocks for high-performance electronics and catalysis owing to their unique width-dependent bandgap and ample lone pair electrons on both sides of GNR, respectively, over the graphene nanosheet counterpart. However, it remains challenging to mass-produce kilogram-scale GNRs to render their practical applications. More importantly, the ability to intercalate nanofillers of interest within GNR enables in-situ large-scale dispersion and retains structural stability and properties of nanofillers for enhanced energy conversion and storage. This, however, has yet to be largely explored. Herein, we report a rapid, low-cost freezing-rolling-capillary compression strategy to yield GNRs at a kilogram scale with tunable interlayer spacing for situating a set of functional nanomaterials for electrochemical energy conversion and storage. Specifically, GNRs are created by sequential freezing, rolling, and capillary compression of large-sized graphene oxide nanosheets in liquid nitrogen, followed by pyrolysis. The interlayer spacing of GNRs can be conveniently regulated by tuning the amount of nanofillers of different dimensions added. As such, heteroatoms; metal single atoms; and 0D, 1D, and 2D nanomaterials can be readily in-situ intercalated into the GNR matrix, producing a rich variety of functional nanofiller-dispersed GNR nanocomposites. They manifest promising performance in electrocatalysis, battery, and supercapacitor due to excellent electronic conductivity, catalytic activity, and structural stability of the resulting GNR nanocomposites. The freezing-rolling-capillary compression strategy is facile, robust, and generalizable. It renders the creation of versatile GNR-derived nanocomposites with adjustable interlay spacing of GNR, thereby underpinning future advances in electronics and clean energy applications.

3.
Exp Cell Res ; 439(1): 114076, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38719174

RESUMEN

Glioblastoma (GBM) is a common primary central nervous system tumor. The molecular mechanisms of glioma are unknown, and the prognosis is poor. Therefore, exploring the underlying mechanisms and screening for new prognostic markers and therapeutic targets is crucial. We utilized the weighted gene co-expression network analysis (WGCNA), Differentially Expressed Genes (DEGs), and LASSO-COX analysis to identify three target genes. Next, we constructed and evaluated a prognostic model, screening out COL8A1 as a risk gene. Through a sequence of cellular functional experiments, in vivo studies, and RNA sequencing, we delved into exploring the functional effects and molecular mechanisms of COL8A1 on GBM cells. Finally, the correlation between COL8A1 and tumor immune cells and different inflammatory responses was analyzed. Immunohistochemistry experiments revealed the influence of COL8A1 on macrophage polarization. The COL8A1 expression level was associated with the grade, prognosis, and tumor microenvironment (TME) of glioma. Functional experiments showed that COL8A1 inhibited GBM cell apoptosis and promoted migration, invasion, and proliferation in vitro and in vivo. We also found that COL8A1 promotes the epithelial-mesenchymal transition process and may mediate the activation of the ERK pathway through SHC1. In addition, immune infiltration analysis showed that COL8A1 was closely associated with macrophages in glioma tissues, significantly suppressing the signaling of M1-like -type macrophages and enhancing the signaling of M2-like -type macrophages. COL8A1 was first found to be associated with prognosis, progression, and immune microenvironment of glioma and may serve as a new marker of prognosis and a therapeutic target.


Asunto(s)
Biomarcadores de Tumor , Neoplasias Encefálicas , Movimiento Celular , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Glioma , Microambiente Tumoral , Animales , Femenino , Humanos , Masculino , Ratones , Apoptosis/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Transición Epitelial-Mesenquimal/genética , Glioblastoma/patología , Glioblastoma/genética , Glioblastoma/metabolismo , Glioma/genética , Glioma/patología , Glioma/metabolismo , Ratones Desnudos , Pronóstico , Microambiente Tumoral/genética
4.
IUBMB Life ; 76(3): 140-160, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37728571

RESUMEN

The molecular mechanisms of glioblastoma (GBM) are unclear, and the prognosis is poor. Spinster homolog 2 (SPNS2) is reportedly involved in pathological processes such as immune response, vascular development, and cancer. However, the biological function and molecular role of SPNS2 in GBM are unclear. SPNS2 is aberrantly low expressed in glioma. Survival curves, risk scores, prognostic nomograms, and univariate and multifactorial Cox regression analyses showed that SPNS2 is an independent prognostic indicator significantly associated with glioma progression and prognosis. Cell function assays and in vivo xenograft transplantation were performed that downregulation of SPNS2 promoted GBM cell growth, migration, invasion, epithelial-mesenchymal transition (EMT), anti-apoptosis, drug resistance, and stemness, while overexpression of SPNS2 had the opposite effect. Meanwhile, the functional enrichment and signaling pathways of SPNS2 in the Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and RNA sequencing were analyzed by Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene set enrichment analysis (GSEA). The above results were related to the inhibition of the PTEN/PI3K/AKT pathway by SPNS2. In addition, we predicted that SPNS2 is closely associated with immune infiltration in the tumor microenvironment by four immune algorithms, ESTIMATE, TIMER, CIBERSORT, and QUANTISEQ. In particular, SPNS2 was negatively correlated with the infiltration of most immune cells, immunomodulators, and chemokines. Finally, single-cell sequencing analysis also revealed that SPNS2 was remarkably correlated with macrophages, and downregulation of SPNS2 promotes the expression of M2-like macrophages. This study provides new evidence that SPNS2 inhibits malignant progression, stemness, and immune infiltration of GBM cells through PTEN/PI3K/AKT pathway. SPNS2 may become a new diagnostic indicator and potential immunotherapeutic target for glioma.


Asunto(s)
Glioblastoma , Glioma , Humanos , Glioblastoma/patología , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Regulación Neoplásica de la Expresión Génica , Glioma/patología , Microambiente Tumoral/genética , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo
5.
FASEB J ; 37(1): e22688, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36468780

RESUMEN

Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies. Vasorin (VASN) has been reported to be critical in tumor development and angiogenesis. However, VASN has not been reported in CRC, and its role is unclear. In this study, VASN expression is upregulated in CRC compared with the normal tissues, and VASN expression positively correlates with N stage and poor overall survival by analysis of different datasets and 32 CRC clinicopathologic samples. Overexpression of VASN significantly promotes CRC cell progression, including proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), while knockdown of VASN inhibits CRC progression. We found that VASN was associated with the YAP/TAZ and PI3K/AKT pathways by gene set enrichment analysis (GSEA) and gene ontology (GO) analysis. Notably, western blotting, immunofluorescence staining and co-immunofluorescence (co-IP) confirmed that VASN could interact with YAP and activate the YAP/TAZ and PTEN/PI3K/AKT pathways, and knockdown of YAP reversed this effect. Importantly, our findings indicate that VASN interacts with YAP to inhibit YAP phosphorylation and stimulates CRC proliferation, migration, and invasion through activation of the YAP/TAZ-TEAD target gene CTGF and PTEN/PI3K/AKT pathways. Our results also show that knockdown of YAP reverses the cellular phenotype induced by increased VASN. In conclusion, our study reveals that VASN acts as an oncogene to stimulate tumor progression in CRC, providing new insights into the molecular mechanisms of CRC development and representing a possible novel biomarker for CRC.


Asunto(s)
Neoplasias Colorrectales , Proteínas Proto-Oncogénicas c-akt , Humanos , Fosfatidilinositol 3-Quinasas , Oncogenes , Transducción de Señal , Neoplasias Colorrectales/genética , Proteínas Portadoras , Proteínas de la Membrana
6.
BMC Ophthalmol ; 24(1): 262, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38898418

RESUMEN

BACKGROUND: Dry eye is a chronic and multifactorial ocular surface disease caused by tear film instability or imbalance in the microenvironment of the ocular surface. It can lead to various discomforts such as inflammation of the ocular surface and visual issues. However, the mechanism of dry eye is not clear, which results in dry eye being only relieved but not cured in clinical practice. Finding multiple environmental pathways for dry eye and exploring the pathogenesis of dry eye have become the focus of research. Studies have found that changes in microbiota may be related to the occurrence and development of dry eye disease. METHODS: Entered the keywords "Dry eye", "Microbiota", "Bacteria" through PUBMED, summarised the articles that meet the inclusion criteria and then filtered them while the publication time range of the literature was defined in the past 5 years, with a deadline of 2023.A total of 13 clinical and 1 animal-related research articles were screened out and included in the summary. RESULTS: Study found that different components of bacteria can induce ocular immune responses through different receptors present on the ocular surface, thereby leading to an imbalance in the ocular surface microenvironment. Changes in the ocular surface microbiota and gut microbiota were also found when dry eye syndrome occurs, including changes in diversity, an increase in pro-inflammatory bacteria, and a decrease in short-chain fatty acid-related bacterial genera that produce anti-inflammatory effects. Fecal microbiota transplantation or probiotic intervention can alleviate signs of inflammation on the ocular surface of dry eye animal models. CONCLUSIONS: By summarizing the changes in the ocular surface and intestinal microbiota when dry eye occurs, it is speculated and concluded that the intestine may affect the occurrence of eye diseases such as dry eye through several pathways and mechanisms, such as the occurrence of abnormal immune responses, microbiota metabolites- intervention of short-chain fatty acids, imbalance of pro-inflammatory and anti-inflammatory factors, and release of neurotransmitters, etc. Analyzing the correlation between the intestinal tract and the eyes from the perspective of microbiota can provide a theoretical basis and a new idea for relieving dry eyes in multiple ways in the future.


Asunto(s)
Síndromes de Ojo Seco , Microbioma Gastrointestinal , Síndromes de Ojo Seco/metabolismo , Síndromes de Ojo Seco/microbiología , Humanos , Microbioma Gastrointestinal/fisiología , Animales , Lágrimas/metabolismo
7.
Angew Chem Int Ed Engl ; : e202408914, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38957932

RESUMEN

Dual-atom catalysts (DACs) have been proposed to break the limitation of single-atom catalysts (SACs) in the synergistic activation of multiple molecules and intermediates, offering an additional degree of freedom for catalytic regulation. However, it remains a challenge to synthesize DACs with high uniformity, atomic accuracy, and satisfactory loadings. Herein, we report a facile cascade synthetic strategy for DAC via precise electrostatic interaction control and neighboring vacancy construction. We synthesized well-defined, uniformly dispersed dual Fe sites which were connected by two nitrogen bonds (denoted as Fe-N2-Fe). The as-synthesized DAC exhibited superior catalytic performances towards oxygen reduction reaction, including good half-wave potential (0.91 V), high kinetic current density (21.66 mA cm-2), and perfect durability. Theoretical calculation revealed that the DAC structure effectively tunes the oxygen adsorption configuration and decreases the cleavage barrier, thereby improving the catalytic kinetics. The DAC-based zinc-air batteries exhibited impressive power densities of 169.8 and 52.18 mW cm-2 at 25 oC and -40 oC, which is 1.7 and 2.0 times higher than those based on Pt/C+Ir/C, respectively. We also demonstrated the universality of our strategy in synthesizing other M-N2-M DACs (M= Co, Cu, Ru, Pd, Pt, and Au), facilitating the construction of a DAC library for different catalytic applications.

8.
Mol Carcinog ; 62(2): 174-184, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36321407

RESUMEN

Colorectal cancer (CRC) is the third frequent cancer and second leading reason of cancer-related mortality all over the globe. Saponins from Platycodi radix (SPR) and microRNAs (miRNAs) have been reported to regulate CRC cell progression. Real-time quantitative polymerase chain reaction (RT-qPCR) detected miR-181c-5p, miR-181d-5p, and RBM47 expression level. Cell counting kit-8 (CCK-8), 5-ethynyl-20-deoxyuridine (EdU), colony formation, transwell, and wound healing assays validated that miR-181c-5p and miR-181d-5p promote CRC cell proliferation, migration and invasion and SPR exerts opposite effects. Cignal Finder Reporter Array and western blot proved that the activity of PI3K/AKT pathway was decreased by RBM47 overexpression. RNA pulldown, luciferase reporter, and RNA-binding protein immunoprecipitation (RIP) assays proved the interaction between miR-181c/d-5p and RBM47, and RBM47 and PTEN. Rescue experiments were carried out to validate that RBM47 reverses the influence of miR-181c/d-5p on the progression of CRC cells. The stability of PTEN was probed by real-time quantitative polymerase chain reaction in CRC cells treated with Actinomycin D (Act D). To be concluded, SPR inactivates PI3K/AKT signaling pathway to suppress CRC cell proliferation, invasion, and migration via miR-181c/d-5p/RBM47. Elucidating the mechanisms of SPR underlying CRC may offer novel insight into CRC treatment.


Asunto(s)
Neoplasias Colorrectales , MicroARNs , Saponinas , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Saponinas/farmacología , Transducción de Señal , MicroARNs/genética , MicroARNs/metabolismo , Proliferación Celular/genética , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Movimiento Celular/fisiología , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo
9.
Environ Res ; 228: 115909, 2023 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-37060989

RESUMEN

Polyacrylamide (PAM) is the most commonly used coagulant aid in coagulation-ultrafiltration (C-UF) systems; however, its hydrolyzed monomer is harmful to the human nervous system. In this study, laminarin (LA), was extracted from Laminaria japonica and used as a novel coagulant aid to improve coagulation efficiency and reduce membrane fouling during the C-UF process. Optimal LA usage conditions were systematically examined and compared with those of PAM to evaluate their potential for industrial applications. The results revealed that coagulation efficiency could be enhanced by 15-35% with moderate LA addition, which exhibited comparable aid effects to PAM. LA exhibited the highest coagulation aid effect at pH 8-9, and under this condition, turbidity and natural organic matter (NOM) removal achieved 82% and 54%, respectively. Compared with a one-time LA dosing strategy, the pollutant removal capacity of batch dosing was superior. Even in lower water temperatures (5-15 °C), coagulation efficiency was still satisfied, which exhibited a good practical application perspective. The coagulation aid role of LA should be attributed to its long-chain molecular structure, which enhances the bridging role between micro flocs and assists floc growth, thus facilitating the formation of large flocs. In addition, LA adsorption on floc surface was conducive to the direct electrostatic repulsion effect of electronegative membrane, which resulted in a more porous cake layer and higher membrane flux. Therefore, LA exhibits excellent application potential for eliminating NOM while simultaneously reducing membrane fouling through the C-UF process.


Asunto(s)
Ultrafiltración , Purificación del Agua , Humanos , Ultrafiltración/métodos , Purificación del Agua/métodos , Membranas Artificiales , Glucanos
10.
BMC Pulm Med ; 23(1): 99, 2023 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-36964522

RESUMEN

BACKGROUND: Sex-related differences in cancer epidemiology, tumor biology, immune system activity, and pharmacogenomics have been suggested to be important considerations for precision cancer control. Here we elucidated systematically sex biases in genetic variants, gene expression profiles, and immunological landscapes of lung adenocarcinoma patients (LUADs) with different ancestry and smoking status. METHODS: Somatic mutation and mRNA expression data of Asian and Non-Asian LUADs were obtained from public databases. Sex-biased genetic mutations, gene expression, biological pathways, and immune infiltration were identified in the context of smoking status and race. RESULTS: Among nonsmokers, male-biased mutations were prevalent in Asian LUADs, while few sex-biased mutations were detected in Non-Asian LUADs. EGFR was the only mutation whose frequency was significantly higher in females than males in both Asian and Non-Asian nonsmokers. More genes exhibited sex-biased expression in Non-Asian LUADs compared to Asian LUADs. Moreover, genes distinctly expressed in females were mainly related to immune-related pathways, whereas those in males were more involved in activation of DNA repair, E2F_targets, and MYC_targets pathways. We also detected sex-specific immune infiltration in the context of genetic variation. In EGFR-mutant LUADs, males had a significantly increased infiltration of CD8 + T cells, whereas resting CD4 + memory T cells were more abundant in females. Additionally, in KRAS-mutant LUADs, CD8 + and CD4 + T cells were more abundant in females than males. In addition, we detected all female patients with high SCGB3A2 expression were exclusively sensitive to immunotherapy, while this phenomenon was not observed in male patients. CONCLUSIONS: Our findings provided evidence that sex-related molecular and cellular components are involved in shaping tumor distinct genetic and immune features, which might have important impact on personalized targeted and immune therapy.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Factores Sexuales , Fumar , Femenino , Humanos , Masculino , Adenocarcinoma del Pulmón/genética , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Mutación , Pueblo Asiatico , Etnicidad
11.
J Cell Mol Med ; 26(10): 2908-2920, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35384279

RESUMEN

Spermatogenesis is a cyclical process in which different generations of spermatids undergo a series of developmental steps at a fixed time and finally produce spermatids. Here, we report that overexpression of PD-L1 (B7 homolog1) in the testis causes sperm developmental disorders and infertility in male mice, with severe malformation and sloughing during spermatid development, characterized by disorganized and collapsed seminiferous epithelium structure. PD-L1 needs to be simultaneously expressed on Sertoli cells and spermatogonia to cause spermatogenesis failure. After that, we excluded the influence of factors such as the PD-L1 receptor and humoral regulation, confirming that PD-L1 has an intrinsic function to interact with PD-L1. Studies have shown that PD-L1 not only serves as a ligand but also plays a receptor-like role in signal transduction. PD-L1 interacts with PD-L1 to affect the adhesive function of germ cells, causing malformation and spermatid sloughing. Taken together, these results indicate that PD-L1 can interact with PD-L1 to cause germ cell detachment and male infertility.


Asunto(s)
Antígeno B7-H1 , Túbulos Seminíferos , Animales , Antígeno B7-H1/genética , Masculino , Ratones , Células de Sertoli , Espermatogénesis/genética , Espermatogonias , Testículo
12.
Kidney Blood Press Res ; 47(5): 329-340, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35249038

RESUMEN

BACKGROUND: Circular RNAs (circRNAs) were demonstrated to have roles in the carcinogenesis of renal cell carcinoma (RCC). Hence, this work aimed to determine the functions and molecular mechanism of circ_0037866 in regulating the progression of RCC. METHODS: Quantitative real-time polymerase chain reaction and Western blotting were used to detect the levels of genes and proteins. In vitro assays, including colony formation, 5-ethynyl-2'-deoxyuridine, flow cytometry, transwell assays, and in vivo tumor formation, were conducted to investigate the effects of circ_0037866 on RCC tumorigenesis. Dual-luciferase reporter assay, RNA pull-down, and RNA immunoprecipitation assay were used to confirm the interaction between miR-384 and circ_0037866 or Chromobox 5 (CBX5). RESULTS: Circ_0037866 is a stable circRNA and was found to be increased in RCC tissues and cells. Functionally, circ_0037866 silencing suppressed RCC cell survival, invasion, and migration in vitro, and impeded RCC cell tumorigenesis in the subcutaneous xenograft model. Mechanistically, circ_0037866 could function as a sponge for miR-384 to elevate the expression of its target CBX5. Furthermore, a series of rescue experiments showed that miR-384 inhibition reversed the anticancer effects of circ_0037866 knockdown on RCC cells; besides that, miR-384 restoration suppressed RCC cell growth and mobility, which were attenuated by CBX5 overexpression. CONCLUSION: Circ_0037866 knockdown restrains the tumorigenesis of RCC by miR-384/CBX5, revealing a promising molecular target for RCC therapy.


Asunto(s)
Carcinoma de Células Renales , Homólogo de la Proteína Chromobox 5 , Neoplasias Renales , MicroARNs , ARN Circular , Carcinogénesis/genética , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Proliferación Celular , Homólogo de la Proteína Chromobox 5/genética , Homólogo de la Proteína Chromobox 5/metabolismo , Femenino , Humanos , Neoplasias Renales/genética , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , Masculino , MicroARNs/genética , MicroARNs/metabolismo , ARN Circular/genética , ARN Circular/metabolismo
13.
Clin Exp Pharmacol Physiol ; 49(12): 1281-1293, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36050267

RESUMEN

Programmed death ligand 1 (PD-L1) is widely known as an immune checkpoint, and immunotherapy through the inhibition of checkpoint molecules has become an important component in the successful treatment of tumours via programmed death 1 (PD-1)/PD-L1 signalling pathways. However, its biological functions and expression profile in colorectal cancer (CRC) are elusive. We previously found that PD-L1 can bind to PD-L1 and cause cell detachment. However, the detailed molecular mechanisms of how PD-L1 binds to PD-L1 and how it transmits signals to the cell remain unclear. In this study, we disclosed that PD-L1 expression was dramatically upregulated in CRC compared to normal tissues. Ectopic expression of PD-L1 inhibits cell adhesive capacity and promotes cell migration in CRC cell lines, while silencing PD-L1 had the opposite effects and suppressed invasion and proliferation. Mechanistically, PD-L1 was found to promote epithelial-mesenchymal transition (EMT) through the ERK signalling molecule pathway and interacted with the 1-86 aa fragment of KRAS to transduce signals. Collectively, our study demonstrated the role of PD-L1 after binding to PD-L1 in CRC, thereby providing a new theoretical basis for further improving immunotherapy with anti-PD-L1 antibodies.


Asunto(s)
Antígeno B7-H1 , Neoplasias Colorrectales , Humanos , Antígeno B7-H1/metabolismo , Movimiento Celular , Neoplasias Colorrectales/patología , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Quinasas de Proteína Quinasa Activadas por Mitógenos/farmacología , Transducción de Señal , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Proteínas ras/metabolismo
14.
Nano Lett ; 21(5): 2248-2254, 2021 03 10.
Artículo en Inglés | MEDLINE | ID: mdl-33599510

RESUMEN

Platinum nanocrystals featuring a multiply twinned structure and uniform sizes below 5 nm are superb catalytic materials, but it is difficult to synthesize such particles owing to the high twin-boundary energy (166 mJ/m2) of Pt. Here, we report a simple route to the synthesis of such nanocrystals by selectively growing them from the vertices of Pd icosahedral seeds. The success of this synthesis critically depends on the introduction of Br- ions to slow the reduction kinetics of the Pt(II) precursor while limiting the surface diffusion of Pt adatoms by conducting the synthesis at 30 °C. Owing to the small size and multiply twinned structure of Pt dots, the as-obtained Pd-Pt nanocrystals show remarkably enhanced activity and durability toward oxygen reduction, with a mass activity of 1.23 A mg-1Pt and a specific activity of 0.99 mA cm-2Pt, which are 8.2 and 4.5 times as high as those of the commercial Pt/C.

15.
Nano Lett ; 20(10): 7662-7669, 2020 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-32881530

RESUMEN

The ability to restrict the shuttle of lithium polysulfide (LiPSn) and improve the utilization efficiency of sulfur represents an important endeavor toward practical application of lithium-sulfur (Li-S) batteries. Herein, we report the crafting of a robust 3D graphene-wrapped, nitrogen-doped, highly mesoporous carbon/sulfur (G-NHMC/S) hierarchical aerogel as an effective polysulfide confinement matrix for a highly stable Li-S battery. Rich polar sites of NHMC firmly anchor LiPSn on the matrix surface. Porous NHMC provides ample space for accommodating sulfur and cushioning its volume expansion. Moreover, graphene wrapped on NHMC/S not only physically hinders the LiPSn shuttle but also interconnects the isolated NHMC/S, thus increasing electron transfer rate. Taken together, triple confinement of G-NHMC/S aerogel synergistically retains the soluble LiPSn and displays a specific capacity of 1322 mAh g-1 and 1000-cycle life. As such, rationally designed 3D carbon/sulfur aerogel affords a unique platform to impart high energy density and stable electrodes for energy storage devices.

16.
Molecules ; 26(22)2021 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-34834141

RESUMEN

Solar fuel generation from thermochemical H2O or CO2 splitting is a promising and attractive approach for harvesting fuel without CO2 emissions. Yet, low conversion and high reaction temperature restrict its application. One method of increasing conversion at a lower temperature is to implement oxygen permeable membranes (OPM) into a membrane reactor configuration. This allows for the selective separation of generated oxygen and causes a forward shift in the equilibrium of H2O or CO2 splitting reactions. In this research, solar-driven fuel production via H2O or CO2 splitting with an OPM reactor is modeled in isothermal operation, with an emphasis on the calculation of the theoretical thermodynamic efficiency of the system. In addition to the energy required for the high temperature of the reaction, the energy required for maintaining low oxygen permeate pressure for oxygen removal has a large influence on the overall thermodynamic efficiency. The theoretical first-law thermodynamic efficiency is calculated using separation exergy, an electrochemical O2 pump, and a vacuum pump, which shows a maximum efficiency of 63.8%, 61.7%, and 8.00% for H2O splitting, respectively, and 63.6%, 61.5%, and 16.7% for CO2 splitting, respectively, in a temperature range of 800 °C to 2000 °C. The theoretical second-law thermodynamic efficiency is 55.7% and 65.7% for both H2O splitting and CO2 splitting at 2000 °C. An efficient O2 separation method is extremely crucial to achieve high thermodynamic efficiency, especially in the separation efficiency range of 0-20% and in relatively low reaction temperatures. This research is also applicable in other isothermal H2O or CO2 splitting systems (e.g., chemical cycling) due to similar thermodynamics.

17.
Nanotechnology ; 30(21): 214002, 2019 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-30865590

RESUMEN

An advanced hierarchically porous nanosheets-constructed three-dimensional (3D) carbon material (HPNSC) is prepared by using low-cost agricultural waste-nelumbium seed-pods as the precursor, and potassium hydroxide (KOH) as the activator. The as-prepared HPNSC material has a hierarchically porous nanosheets-constructed structure with 3D carbon nanosheet network morphology, which can enable fast and efficient transfer of Li+/Na+/H+ during charge-discharge process. The assembled HPNSC//HPNSC symmetric supercapacitors exhibit an improved energy density of 41.3 W h kg-1 with a power density of 180 W kg-1 in 1 mol l-1 Na2SO4 electrolyte. The energy density can still be maintained at 16.3 W h kg-1 even if the power density is increased to 9000 W kg-1. When acting as the reversible electrode for lithium ion batteries, this HPNSC material can achieve a high specific capacity of 1246 mA h g-1 at 0.1 A g-1. Moreover, sodium ion battery with HPNSC electrode exhibits excellent cycling performance of 161.8 mA h g-1 maintained even after being cycled 3350 times. The electrochemical performances clearly indicate that the HPNSC developed in this work is a very promising energy storage electrode material, and can further provide new insights for designing and developing highly porous materials for energy storage in other fields.

18.
Nano Lett ; 18(12): 8062-8069, 2018 12 12.
Artículo en Inglés | MEDLINE | ID: mdl-30499674

RESUMEN

We introduce the concept of and a generic approach to realizing extreme Huygens' metasurfaces by bridging the concepts of Huygens' conditions and optical bound states in the continuum. This novel paradigm allows the creation of Huygens' metasurfaces with quality factors that can be tuned over orders of magnitude, generating extremely dispersive phase modulation. We validate this concept with a proof-of-concept experiment at the near-infrared wavelengths, demonstrating all-dielectric Huygens' metasurfaces with different quality factors. Our study points out a practical route for controlling the radiative decay rate while maintaining the Huygens' condition, complementing existing Huygens' metasurfaces whose bandwidths are relatively broad and complicated to tune. This novel feature can provide new insight for various applications, including optical sensing, dispersion engineering and pulse shaping, tunable metasurfaces, metadevices with high spectral selectivity, and nonlinear meta-optics.

19.
J Cell Biochem ; 119(4): 3304-3316, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29125890

RESUMEN

Gastric cancer (GC) is the fourth common cancer and second leading cause of cancer-related mortality in the world. WD repeat domain 5 (WDR5) has been identified that its functions as an important role in various biological functions through the epigenetic regulation of gene transcription. However, the oncogenic effect of WDR5 in gastric cancer remains largely unknown. In this study, we investigated the role of WDR5 in gastric cancer genesis. We found that WDR5 expression is increased in gastric cancer patients. Through survival analysis, we found that high expression of WDR5 is associated with high risk gastric cancer; patients who with WDR5 high expression have poor survival rate compared with those who with WDR5 low expression. To make further investigation, we identified that WDR5 is targeted for cell cycle arrest by the Cyclin D1 in a process that is regulated by H3K4me3. Moreover, over-expression of WDR5 promotes cell proliferation, induces S/G2/M arrest in cell cycle, and promotes the expression of WDR5 targets, as well as that of H3K4me3 on the promoter of its targets. Inversely, WDR5 knockdown by shRNA inhibits cell proliferation, reverses S/G2/M arrest in cell cycle, and suppresses the expression of WDR5 targets, as well as that of H3K4me3. We also observed the positive correlation of WDR5 expression with its target in the cohort study of gastric patients. Taken together, our data reveal that WDR5 may have oncogenic effect and WDR5-mediated H3K4 methylation plays an important role in gastric cancer.


Asunto(s)
Ciclina D1/genética , N-Metiltransferasa de Histona-Lisina/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Regulación hacia Arriba , Animales , Línea Celular Tumoral , Proliferación Celular , Ciclina D1/metabolismo , Epigénesis Genética , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica , N-Metiltransferasa de Histona-Lisina/metabolismo , Histonas/metabolismo , Humanos , Péptidos y Proteínas de Señalización Intracelular , Ratones , Trasplante de Neoplasias , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Regiones Promotoras Genéticas , Neoplasias Gástricas/metabolismo , Análisis de Supervivencia
20.
Phys Rev Lett ; 121(19): 193903, 2018 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-30468599

RESUMEN

We reveal that metasurfaces created by seemingly different lattices of (dielectric or metallic) meta-atoms with broken in-plane symmetry can support sharp high-Q resonances arising from a distortion of symmetry-protected bound states in the continuum. We develop a rigorous theory of such asymmetric periodic structures and demonstrate a link between the bound states in the continuum and Fano resonances. Our results suggest the way for smart engineering of resonances in metasurfaces for many applications in nanophotonics and metaoptics.

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