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1.
Exp Cell Res ; 439(1): 114076, 2024 May 07.
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.

2.
PLoS One ; 19(4): e0301585, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38625891

RESUMEN

In order to solve the problem of coordinated development among mining economy, social governance and environmental conservation in global resource-based cities, we choose Guangxi Zhuang Autonomous Region as the research area. The advantage of resource endowment and resource industry was measured by location quotient and input-output method. The panel data related to mining governance from 2010 to 2021 were selected to build the evaluation and coupling analysis model between mining economic, social governance and environmental conservation, and the spatial-temporal heterogeneity and coupling effect of them were analyzed by comprehensive empowerment evaluation, spatial autocorrelation analysis and barrier degree methods. The results show that: (1) Except for the overall upward trend of social governance, the development level of mining economy and environmental conservation are basically stable; (2) The resource-rich areas have obvious mining economic advantages, and the central cities have good social governance capabilities, and the environmental conservation effectiveness is uncertain; (3) The coupling effect between mining economy and social governance is stronger than that between mining economy and environment conservation, and the synergistic coupling effect of the three is relatively random. Finally, we put forward some policy response strategies to Guangxi, and theoretical and practical reference would be provided for resource-based cities around the world.


Asunto(s)
Desarrollo Económico , Urbanización , China , Ciudades , Industrias , Conservación de los Recursos Naturales
3.
Sci Bull (Beijing) ; 69(8): 1109-1121, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38413331

RESUMEN

Hydrogen is widely regarded as a sustainable energy carrier with tremendous potential for low-carbon energy transition. Solar photovoltaic-driven water electrolysis (PV-E) is a clean and sustainable approach of hydrogen production, but with major barriers of high hydrogen production costs and limited capacity. Steam methane reforming (SMR), the state-of-the-art means of hydrogen production, has yet to overcome key obstacles of high reaction temperature and CO2 emission for sustainability. This work proposes a solar thermo-electrochemical SMR approach, in which solar-driven mid/low-temperature SMR is combined with electrochemical H2 separation and in-situ CO2 capture. The feasibility of this method is verified experimentally, achieving an average methane conversion of 96.8% at a dramatically reduced reforming temperature of 400-500 °C. The underlying mechanisms of this method are revealed by an experimentally calibrated model, which is further employed to predict its performance for thermo-electrochemical hydrogen production. Simulation results show that a net solar-to-H2 efficiency of 26.25% could be obtained at 500 °C, which is over 11 percentage points higher than that of PV-E; the first-law thermodynamic efficiency reaches up to 63.27% correspondingly. The enhanced efficiency also leads to decreased fuel consumption and lower CO2 emission of the proposed solar-driven SMR system. Such complementary conversion of solar PV electricity, solar thermal energy, and low-carbon fuel provides a synergistic and efficient means of sustainable H2 production with potentially long-term solar energy storage on a vast scale.

4.
Biomaterials ; 307: 122515, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38401481

RESUMEN

Implant-associated infections (IAIs) pose a significant threat to orthopedic surgeries. Bacteria colonizing the surface of implants disrupt bone formation-related cells and interfere with the osteoimmune system, resulting in an impaired immune microenvironment and osteogenesis disorders. Inspired by nature, a zeolitic imidazolate framework (ZIF)-sealed smart drug delivery system on Ti substrates (ZSTG) was developed for the "natural-artificial dual-enzyme intervention (NADEI)" strategy to address these challenges. The subtle sealing design of ZIF-8 on the TiO2 nanotubes ensured glucose oxidase (GOx) activity and prevented its premature leakage. In the acidic infection microenvironment, the degradation of ZIF-8 triggered the rapid release of GOx, which converted glucose into H2O2 for disinfection. The Zn2+ released from degraded ZIF-8, as a DNase mimic, can hydrolyze extracellular DNA, which further enhances H2O2-induced disinfection and prevents biofilm formation. Importantly, Zn2+-mediated M2 macrophage polarization significantly improved the impaired osteoimmune microenvironment, accelerating bone repair. Transcriptomics revealed that ZSTG effectively suppressed the inflammatory cascade induced by lipopolysaccharide while promoting cell proliferation, homeostasis maintenance, and bone repair. In vitro and in vivo results confirmed the superior anti-infective, osteoimmunomodulatory, and osteointegrative capacities of the ZSTG-mediated NADEI strategy. Overall, this smart bionic platform has significant potential for future clinical applications to treat IAIs.


Asunto(s)
Antiinfecciosos , Zeolitas , Oseointegración , Peróxido de Hidrógeno/farmacología , Macrófagos , Antiinfecciosos/farmacología , Osteogénesis
5.
Nat Commun ; 15(1): 1767, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38409177

RESUMEN

Developing efficient and economical electrocatalysts for acidic oxygen evolution reaction (OER) is essential for proton exchange membrane water electrolyzers (PEMWE). Cobalt oxides are considered promising non-precious OER catalysts due to their high activities. However, the severe dissolution of Co atoms in acid media leads to the collapse of crystal structure, which impedes their application in PEMWE. Here, we report that introducing acid-resistant Ir single atoms into the lattice of spinel cobalt oxides can significantly suppress the Co dissolution and keep them highly stable during the acidic OER process. Combining theoretical and experimental studies, we reveal that the stabilizing effect induced by Ir heteroatoms exhibits a strong dependence on the distance of adjacent Ir single atoms, where the OER stability of cobalt oxides continuously improves with decreasing the distance. When the distance reduces to about 0.6 nm, the spinel cobalt oxides present no obvious degradation over a 60-h stability test for acidic OER, suggesting potential for practical applications.

6.
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
7.
Diagn Microbiol Infect Dis ; 108(2): 116136, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38041889

RESUMEN

The antigen rapid diagnostic test (Ag-RDT) is an assay kit for detecting the SARS-COV-2 nucleocapsid proteins, based on the colloidal gold method.Accurate diagnosis has an important role in limiting the transmission of SARS-COV-2, and also helps patients to receive earlier treatment .The object of this study was to perform the clinical evaluation of a novel Ag-RDTs with samples collected from two different swabs.DEEPBLUE®COVID-19 antigen detection kit used for the examination of the subjects in the experiment.For antigen testing on samples collected with nasal swabs, sensitivity was 91.7 % (95 % CI 83.6-96.6 %) and specificity was 100 %(95 %CI 98.1-100 %).For nasopharyngeal swabs, the sensitivity was 96.8 % (95 % CI 93.6-98.7 %) and the specificity was 100 % (95 % CI 98.2-100 %).Fisher Precision test showed a significant correlation between nasopharyngeal swab Ag-RDTs and nasal swab Ag-RDTs and RT-qPCR test (p-value <0.001).The results showed that the patients use the kit for testing were comparable to the RT-qPCR.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/diagnóstico , Bioensayo , Sensibilidad y Especificidad
8.
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.

9.
Arch Med Sci ; 19(2): 478-487, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37034517

RESUMEN

Introduction: Long non-coding RNAs (lncRNAs) have been implicated in the initiation and progression of malignant tumor. The aim of the present study was to investigate whether LINC00336 contributes to the tumorigenesis of bladder cancer (BCa). Material and methods: LncRNA expression profiling in BCa tissues was analyzed using lncRNA microarray. Cell viability, invasion and apoptosis were detected using CCK8, Transwell and Annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC) double staining, respectively. Results: LncRNA microarray and RT-qPCR revealed that LINC00336 was significantly up-regulated in BCa tissues and cell lines compared with the corresponding control group. Kaplan-Meier and multivariate regression analysis demonstrated that LINC00336 could serve as an independent risk factor for predicting the prognosis of BCa patients. In vitro experimental measurements showed that knockdown of LINC00336 had the ability to block cell proliferation and invasion, as well as to induce cell cycle arrest and apoptosis. Conclusions: These findings indicated that LINC00336 might serve as an oncogene in the initiation and progression of BCa, and LINC00336 may be a valuable and promising therapeutic target for the treatment of BCa.

10.
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
11.
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
12.
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.

13.
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
14.
Sci Total Environ ; 859(Pt 1): 159964, 2023 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-36372177

RESUMEN

China is promoting the production and use of electric vehicles (EVs) to achieve carbon neutrality. However, the shift will drive higher demand and tighter supply of nickel in China. We develop a stock-driven bottom-up dynamic substance flow analysis (SFA) model to simulate the demand trends of various EVs under 3 scenarios, the flow of nickel under 9 scenarios and the amount of recoverable nickel under 27 scenarios in China's EV industry from 2010 to 2050. The results indicate that China's current production capacity and primary reserves of nickel cannot meet the growing nickel demand, especially under the High EVs-LNCT scenarios, and closed-loop nickel recovery from EV batteries can effectively alleviate the demand-supply contradiction. In different scenarios, the annual recycling nickel could cover between 67.7 % and 96.6 % of the demand for EV batteries in 2050, and between 37.9 % and 58.1 % in terms of the cumulative quantity by 2050. When the low nickel battery technology is adopted and the recovery efficiency is rapidly improved, the recovered nickel would meet the demand for EV batteries to the highest degree. Therefore, sufficient attention should be paid to low-nickel battery technology and efficient recycling of spent EV batteries, which is of great significance to ensure the development of EV industry and the availability of nickel in China.


Asunto(s)
Suministros de Energía Eléctrica , Níquel , Reciclaje , Electricidad , Industrias , China
15.
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
16.
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
17.
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
18.
Chemosphere ; 298: 134200, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35278447

RESUMEN

Polyhalogenated carbazoles (PHCZs), are considered as potential persistent organic pollutants (POPs), which have been frequently detected in the environment. However, the altitudinal distribution characteristics and possible sources of PHCZs in high mountain soils are still unknown. The present study was the first to analyze PHCZs in soil samples collected along the eastern slope of Mt. Qionglai (MQ), the east edge of the Tibetan Plateau. The concentration of ΣPHCZs (based on dry weight) ranges from 14.4 to 107 ng/g (median value of 40.9), which was at high end of the range reported in soils and sediments to date in the literature. The composition profiles of PHCZs in the soils of MQ were dominated by 3,6-dichlorocarbazole (36-CCZ), 3-chlorocarbazole (3-CCZ), and 2-bromocarbazole (2-BCZ). The mean TOC-normalized concentrations of ΣPHCZs in soil samples from below-treeline (2092 ng/g TOC) were higher than those from alpine meadow (1124 ng/g TOC), probably due to the forest filter effect. The decreasing trend of the PHCZs TOC-normalized concentrations with altitude shows that accumulation of PHCZs from the alpine meadow samples was not affected by the mountain cold-trapping effect. Significantly positive correlations were observed between the concentrations of more than half of detected PHCZ congeners and TOC. In addition, PHCZs show the potential to represent a class of POPs with the frequent occurrence and wide distribution, as the abundance and environmental behavior of PHCZs are similar to some POPs in MQ.


Asunto(s)
Suelo , Contaminantes Químicos del Agua , Carbazoles/análisis , Monitoreo del Ambiente , Tibet , Contaminantes Químicos del Agua/análisis
19.
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
20.
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.

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