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1.
Adv Sci (Weinh) ; : e2404053, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38973357

RESUMO

Electrochemical CO2 reduction has garnered significant interest in the conversion of sustainable energy to valuable fuels and chemicals. Cu-based bimetallic catalysts play a crucial role in enhancing *CO concentration on Cu sites for efficient C─C coupling reactions, particularly for C2 product generation. To enhance Cu's electronic structure and direct its selectivity toward C2 products, a novel strategy is proposed involving the in situ electropolymerization of a nano-thickness cobalt porphyrin polymeric network (EP-CoP) onto a copper electrode, resulting in the creation of a highly effective EP-CoP/Cu tandem catalyst. The even distribution of EP-CoP facilitates the initial reduction of CO2 to *CO intermediates, which then transition to Cu sites for efficient C─C coupling. DFT calculations confirm that the *CO enrichment from Co sites boosts *CO coverage on Cu sites, promoting C─C coupling for C2+ product formation. The EP-CoP/Cu gas diffusion electrode achieves an impressive current density of 726 mA cm-2 at -0.9 V versus reversible hydrogen electrode (RHE), with a 76.8% Faraday efficiency for total C2+ conversion and 43% for ethylene, demonstrating exceptional long-term stability in flow cells. These findings mark a significant step forward in developing a tandem catalyst system for the effective electrochemical production of ethylene.

2.
Comput Methods Programs Biomed ; 254: 108285, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38964248

RESUMO

BACKGROUND AND OBJECTIVE: In renal disease research, precise glomerular disease diagnosis is crucial for treatment and prognosis. Currently reliant on invasive biopsies, this method bears risks and pathologist-dependent variability, yielding inconsistent results. There is a pressing need for innovative diagnostic tools that enhance traditional methods, streamline processes, and ensure accurate and consistent disease detection. METHODS: In this study, we present an innovative Convolutional Neural Networks-Vision Transformer (CVT) model leveraging Transformer technology to refine glomerular disease diagnosis by fusing spectral and spatial data, surpassing traditional diagnostic limitations. Using interval sampling, preprocessing, and wavelength optimization, we also introduced the Gramian Angular Field (GAF) method for a unified representation of spectral and spatial characteristics. RESULTS: We captured hyperspectral images ranging from 385.18 nm to 1009.47 nm and employed various methods to extract sample features. Initial models based solely on spectral features achieved a accuracy of 85.24 %. However, the CVT model significantly outperformed these, achieving an average accuracy of 94 %. This demonstrates the model's superior capability in utilizing sample data and learning joint feature representations. CONCLUSIONS: The CVT model not only breaks through the limitations of existing diagnostic techniques but also showcases the vast potential of non-invasive, high-precision diagnostic technology in supporting the classification and prognosis of complex glomerular diseases. This innovative approach could significantly impact future diagnostic strategies in renal disease research. CONCISE ABSTRACT: This study introduces a transformative hyperspectral image classification model leveraging a Transformer to significantly improve glomerular disease diagnosis accuracy by synergizing spectral and spatial data, surpassing conventional methods. Through a rigorous comparative analysis, it was determined that while spectral features alone reached a peak accuracy of 85.24 %, the novel Convolutional Neural Network-Transformer (CVT) model's integration of spatial-spectral features via the Gramian Angular Field (GAF) method markedly enhanced diagnostic precision, achieving an average accuracy of 94 %. This methodological innovation not only overcomes traditional diagnostic limitations but also underscores the potential of non-invasive, high-precision technologies in advancing the classification and prognosis of complex renal diseases, setting a new benchmark in the field.

3.
J Chem Theory Comput ; 20(11): 4703-4710, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38825857

RESUMO

In recent years, machine learning (ML) surrogate models have emerged as an indispensable tool to accelerate simulations of physical and chemical processes. However, there is still a lack of ML models that can accurately predict molecular vibrational spectra. Here, we present a highly efficient multitask ML surrogate model termed Vibrational Spectra Neural Network (VSpecNN), to accurately calculate infrared (IR) and Raman spectra based on dipole moments and polarizabilities obtained on-the-fly via ML-enhanced molecular dynamics simulations. The methodology is applied to pyrazine, a prototypical polyatomic chromophore. The VSpecNN-predicted energies are well within the chemical accuracy (1 kcal/mol), and the errors for VSpecNN-predicted forces are only half of those obtained from a popular high-performance ML model. Compared to the ab initio reference, the VSpecNN-predicted frequencies of IR and Raman spectra differ only by less than 5.87 cm-1, and the intensities of IR spectra and the depolarization ratios of Raman spectra are well reproduced. The VSpecNN model developed in this work highlights the importance of constructing highly accurate neural network potentials for predicting molecular vibrational spectra.

4.
RSC Adv ; 14(25): 17434-17439, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38813129

RESUMO

In this study, we developed a D-A type imide derivative based on 1,8-naphthalimide, NI-mPCz, which exhibited outstanding thermally activated delayed fluorescence (TADF) properties. Additionally, it demonstrates characteristics of piezochromic and thermochromic luminescence. The thermochromic luminescence observed is attributed to crystalline transformations occurring during the heating process, as evidenced by differential scanning calorimetry (DSC) and microscopic examinations. Moreover, the good compatibility of NI-mPCz with HeLa cells and its excellent imaging performance indicate its potential for application in the field of biological imaging. These results provide valuable insights for the design and development of new organic electronic and bioimaging materials with high-efficiency TADF characteristics.

5.
Asian J Androl ; 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38319194

RESUMO

Ex vivo tissue culture of the human corpus cavernosum (CC) can be used to explore the tissue structural changes and complex signaling networks. At present, artificial CC-like tissues based on acellular or three-dimensional (3D)-printed scaffolds are used to solve the scarcity of primary penis tissue samples. However, inconvenience and high costs limit the wide application of such methods. Here, we describe a simple, fast, and economical method of constructing artificial CC-like tissue. Human CC fibroblasts (FBs), endothelial cells (ECs), and smooth muscle cells (SMCs) were expanded in vitro and mixed with Matrigel in specific proportions. A large number of bubbles were formed in the mixture by vortexing combined with pipette blowing, creating a porous, spongy, and spatial structure. The CC FBs produced a variety of signaling factors, showed multidirectional differentiation potential, and grew in a 3D grid in Matrigel, which is necessary for CC-like tissue to maintain a porous structure as a cell scaffold. Within the CC-like tissue, ECs covered the surface of the lumen, and SMCs were located inside the trabeculae, similar to the structure of the primary CC. Various cell components remained stable for 3 days in vitro, but the EC content decreased on the 7th day. Wingless/integrated (WNT) signaling activation led to lumen atrophy and increased tissue fibrosis in CC-like tissue, inducing the same changes in characteristics as in the primary CC. This study describes a preparation method for human artificial CC-like tissue that may provide an improved experimental platform for exploring the function and structure of the CC and conducting drug screening for erectile dysfunction therapy.

6.
RSC Adv ; 14(10): 6494-6500, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38390502

RESUMO

Thermally activated delayed fluorescence (TADF) molecules have emerged as a promising class of third-generation organic light-emitting diode (OLED) emitters that can achieve 100% internal quantum efficiency without the use of noble metals. However, the design of high-efficiency red TADF materials has been challenging due to limitations imposed by the energy-gap law. To overcome this challenge, two new TADF emitters, namely, 6-(4-(diphenylamino)phenyl)-2-phenyl-1H-benzo[de]isoquinoline-1,3(2H)-dione (NI-TPA) and 6-(10H-phenothiazin-10-yl)-2-phenyl-1H-benzo[de]-isoquinoline-1,3(2H)-dione (NI-Pz), have been synthesized and characterized. These compounds exhibit strong TADF characteristics with a small energy gap (ΔEST) between the lowest excited singlet and triplet states, short delayed fluorescence lifetimes, high thermal stability, and high photoluminescence quantum yields. The OLED devices fabricated using NI-TPA and NI-Pz as emitters show orange and red electroluminescence with emission peaks at 593 nm and 665 nm, respectively, and maximum external quantum efficiencies (EQEs) of 11.3% and 7.6%, respectively. Furthermore, applying NI-TPA to cell imaging yielded excellent imaging results, indicating the potential of red TADF materials in the field of biological imaging.

7.
Environ Toxicol ; 38(12): 2894-2903, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37551626

RESUMO

BACKGROUND: Cancer stem cells (CSCs) play a key role in tumor cell growth, drug resistance, recurrence, and metastasis. Proanthocyanidins (PC) is widely existed in plants and endowed with powerful antioxidant and anti-aging effects. Interestingly, recent studies have found that PC exhibits the inhibitory effect on tumor growth. However, the role of PC in CSCs of colorectal cancer (CRC) and molecular mechanism remain unclear. METHODS: CCK-8, colony, and tumorsphere formation assay were used to evaluate cancer cell viability and stemness, respectively. Western blotting was used to detect the protein expression. Tumor xenograft experiments were employed to examine the tumorigenicity of CRC cells in nude mice. RESULTS: PC decreased the proliferation of CRC cells (HT29 and HCT-116), and improved the sensitivity of CRC cells to oxaliplatin (L-OHP), as well as inhibited tumor growth in nude mice. Further studies showed that PC also down-regulated CSCs surface molecular and stemness transcriptional factors, while suppressed the formations of tumorspheres and cell colony in CRC. In addition, PC-impaired proteins expressions of p-GSK3ß, ß-catenin and DVL1-3. LiCl, an activator of the Wnt/ß-catenin signaling, rescued PC-induced downregulation of CSCs markers, and reduction of tumorspheres and cell colony formation abilities in CRC cells. Furthermore, the effects of PC on inhibiting cell proliferation and enhancing L-OHP sensitivity were impaired by LiCl. CONCLUSIONS: PC exerted an inhibitory effect on CSCs via Wnt/ß-catenin in CRC, and may be a potential new class of natural drug for CRC treatment.


Assuntos
Neoplasias Colorretais , Proantocianidinas , Animais , Camundongos , Humanos , Linhagem Celular Tumoral , Camundongos Nus , Proantocianidinas/farmacologia , Proantocianidinas/metabolismo , Proantocianidinas/uso terapêutico , beta Catenina/metabolismo , Neoplasias Colorretais/genética , Células-Tronco Neoplásicas/metabolismo , Proliferação de Células , Regulação Neoplásica da Expressão Gênica
8.
Photodiagnosis Photodyn Ther ; 43: 103708, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37482369

RESUMO

BACKGROUND: Cutaneous melanoma, an exceedingly aggressive form of skin cancer, holds the top rank in both malignancy and mortality among skin cancers. In early stages, distinguishing malignant melanomas from benign pigmented nevi pathologically becomes a significant challenge due to their indistinguishable traits. Traditional skin histological examination techniques, largely reliant on light microscopic imagery, offer constrained information and yield low-contrast results, underscoring the necessity for swift and effective early diagnostic methodologies. As a non-contact, non-ionizing, and label-free imaging tool, hyperspectral imaging offers potential in assisting pathologists with identification procedures sans contrast agents. METHODS: This investigation leverages hyperspectral cameras to ascertain the optical properties and to capture the spectral features of malignant melanoma and pigmented nevus tissues, intending to facilitate early pathological diagnostic applications. We further enhance the diagnostic process by integrating transfer learning with deep convolutional networks to classify melanomas and pigmented nevi in hyperspectral pathology images. The study encompasses pathological sections from 50 melanoma and 50 pigmented nevus patients. To accurately represent the spectral variances between different tissues, we employed reflectance calibration, highlighting that the most distinctive spectral differences emerged within the 500-675 nm band range. RESULTS: The classification accuracy of pigmented tumors and pigmented nevi was 89% for one-dimensional sample data and 98% for two-dimensional sample data. CONCLUSIONS: Our findings have the potential to expedite pathological diagnoses, enhance diagnostic precision, and offer novel research perspectives in differentiating melanoma and nevus.


Assuntos
Aprendizado Profundo , Melanoma , Nevo Pigmentado , Fotoquimioterapia , Neoplasias Cutâneas , Humanos , Melanoma/diagnóstico por imagem , Melanoma/patologia , Neoplasias Cutâneas/patologia , Imageamento Hiperespectral , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes , Detecção Precoce de Câncer , Nevo Pigmentado/diagnóstico por imagem , Nevo Pigmentado/patologia , Diagnóstico Diferencial , Melanoma Maligno Cutâneo
9.
Adv Mater ; 35(38): e2303179, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37307384

RESUMO

Electrocatalytic CO2 reduction reaction (CO2 RR) based on molecular catalysts, for example, cobalt porphyrin, is promising to enhance the carbon cycle and mitigate current climate crisis. However, the electrocatalytic performance and accurate evaluations remain problems because of either the low loading amount or the low utilization rate of the electroactive CoN4 sites. Herein a monomer is synthesized, cobalt(II)-5,10,15,20-tetrakis(3,5-di(thiophen-2-yl)phenyl)porphyrin (CoP), electropolymerized onto carbon nanotubes (CNTs) networks, affording a molecular electrocatalyst of 3D microporous nanofilm (EP-CoP, 2-3 nm thickness) with highly dispersed CoN4 sites. The new electrocatalyst shortens the electron transfer pathway, accelerates the redox kinetics of CoN4 sites, and improves the durability of the electrocatalytic CO2 RR. From the intrinsic redox behavior of CoN4 sites, the effective utilization rate is obtained as 13.1%, much higher than that of the monomer assembled electrode (5.8%), and the durability is also promoted dramatically (>40 h) in H-type cells. In commercial flow cells, EP-CoP can achieve a faradic efficiency for CO (FECO ) over 92% at an overpotential of 160 mV. At a higher overpotential of 620 mV, the working current density can reach 310 mA cm-2 with a high FECO of 98.6%, representing the best performance for electrodeposited molecular porphyrin electrocatalysts.

10.
Drug Dev Res ; 84(5): 988-998, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37132439

RESUMO

Colorectal cancer (CRC) is a common tumor with high morbidity and mortality. The use of oxaliplatin (L-OHP) as a first-line treatment for CRC is limited due to chemoresistance. Growing evidence have revealed that the existence of cancer stem-like cells (CSLCs) is one of the important reasons for drug resistance and recurrence of cancers. Dihydroartemisinin (DHA), a derivative of artemisinin, has showed anticancer effects on a variety of malignancies, in addition to its antimalarial effects. However, the effect and mechanism of DHA on CSLCs and chemosensitivity in CRC cells remains unclear. In this study, we found that DHA inhibited cell viability in HCT116 and SW620 cells. Moreover, DHA decreased cell clonogenicity, and improved L-OHP sensitivity. Furthermore, DHA treatment attenuated tumor sphere formation, and the expressions of stem cell surface marker (CD133 and CD44) and stemness-associated transcription factor (Nanog, c-Myc, and OCT4). Mechanistically, the present findings showed that DHA inhibited of AKT/mTOR signaling pathway. The activation of AKT/mTOR signaling reversed DHA-decreased cell viability, clonogenicity, L-OHP resistance, tumor sphere, and expressions of stemness-associated protein in CRC. The inhibitory effect of DHA on tumorigenicity of CRC cells has also been demonstrated in BALB/c nude mice. In conclusion, this study revealed that DHA inhibited CSLCs properties in CRC via AKT/mTOR signaling, suggesting that DHA may be used as a potential therapeutic agent for CRC.


Assuntos
Neoplasias Colorretais , Proteínas Proto-Oncogênicas c-akt , Animais , Camundongos , Oxaliplatina/farmacologia , Oxaliplatina/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Camundongos Nus , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Células-Tronco Neoplásicas , Linhagem Celular Tumoral , Proliferação de Células
11.
Asian J Androl ; 25(6): 662-673, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37202929

RESUMO

Klinefelter syndrome (KS) is the most common genetic cause of human male infertility. However, the effect of the extra X chromosome on different testicular cell types remains poorly understood. Here, we profiled testicular single-cell transcriptomes from three KS patients and normal karyotype control individuals. Among the different somatic cells, Sertoli cells showed the greatest transcriptome changes in KS patients. Further analysis showed that X-inactive-specific transcript ( XIST ), a key factor that inactivates one X chromosome in female mammals, was widely expressed in each testicular somatic cell type but not in Sertoli cells. The loss of XIST in Sertoli cells leads to an increased level of X chromosome genes, and further disrupts their transcription pattern and cellular function. This phenomenon was not detected in other somatic cells such as Leydig cells and vascular endothelial cells. These results proposed a new mechanism to explain why testicular atrophy in KS patients is heterogeneous with loss of seminiferous tubules but interstitial hyperplasia. Our study provides a theoretical basis for subsequent research and related treatment of KS by identifying Sertoli cell-specific X chromosome inactivation failure.


Assuntos
Síndrome de Klinefelter , Células de Sertoli , Animais , Humanos , Masculino , Feminino , Células de Sertoli/metabolismo , Síndrome de Klinefelter/genética , Células Endoteliais , Testículo/metabolismo , Cromossomo X/metabolismo , Mamíferos/genética
12.
Biochem Genet ; 61(5): 1727-1744, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36763221

RESUMO

BACKGROUND: Colorectal cancer (CRC) is one of the major gastrointestinal malignancies threatening human health. More and more studies indicate that circular RNAs (circRNAs) are important regulatory factors of CRC, but the mechanism is still indistinct. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect the expression of circ_0084188, microRNA-769-5p (miR-769-5p), and kinesin family member 20A (KIF20A) in CRC tissues. Kaplan-Meier curve was used to analyze the relationship between circ_0084188 expression and the survival rate of CRC patients. Cell proliferation, viability, apoptosis, migration, and invasion were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, wound-healing, and transwell assays, respectively. The relationship between miR-769-5p and circ_0084188 or KIF20A was detected by a dual-luciferase reporter and RNA pull-down. The effect of circ_0084188 on tumor growth was verified by xenograft studies in vivo. RESULTS: Circ_0084188 and KIF20A were upregulated and miR-769-5p was downregulated in CRC. Circ_0084188 knockdown repressed the proliferation, migration, and invasion of CRC cells, as well as enhanced apoptosis in vitro. Mechanistically, circ_0084188 targeted miR-769-5p, and the reduction of miR-769-5p reversed the effects of circ_0084188 knockdown on cell functional behaviors. KLF20A was a direct miR-769-5p target, and circ_0084188 acted as a sponge for miR-769-5p to regulate the KIF20A level. Moreover, miR-769-5p regulated the functional behaviors of CRC cells by targeting KIF20A. In addition, circ_0084188 knockdown confined the growth of xenograft tumors in vivo. CONCLUSION: Circ_0084188 upregulated the expression of KIF20A to promote the tumorigenesis of CRC through miR-769-5p, providing a new therapeutic target for CRC.


Assuntos
Neoplasias Colorretais , Cinesinas , MicroRNAs , RNA Circular , Humanos , Apoptose , Carcinogênese , Proliferação de Células , Neoplasias Colorretais/genética , Cinesinas/genética , MicroRNAs/genética , RNA Circular/genética
13.
Int J Mol Sci ; 23(23)2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36499213

RESUMO

Injury to corpus cavernosal endothelial cells (CCECs) is an important pathological basis of diabetes mellitus-induced erectile dysfunction (DMED), while low-intensity pulsed ultrasound (LIPUS) has been shown to improve erectile function in DMED. To further understand its therapeutic mechanism of action, in this study, we first demonstrated increased apoptosis and shedding in the CCECs of DMED patients, accompanied by significant mitochondrial injury by immunohistochemistry and electron microscopy of corpus cavernosum tissue. Next, we used advanced glycation end products (AGEs) to simulate the diabetic environment in vitro and found that AGES damaged mitochondria and inhibited angiogenesis in CCECs in a dose-dependent manner, while LIPUS treatment significantly reversed its effects. Mechanistic studies based on transcriptome sequencing showed that LIPUS significantly up-regulated LC3 and PARKIN protein levels in mitochondria, promoted mitophagy, and affected mitochondrial dynamics and reactive oxygen species (ROS) production. In addition, the protective effects of LIPUS were abrogated when mitophagy was inhibited by 3-methyladenine. In summary, LIPUS exerted potent inhibitory effects on AGES-induced CCEC failure via mitophagy, providing a theoretical basis for DMED treatment that encompasses the protection of endothelial structure and function.


Assuntos
Células Endoteliais , Mitofagia , Masculino , Ratos , Animais , Humanos , Ratos Sprague-Dawley , Ondas Ultrassônicas , Produtos Finais de Glicação Avançada
14.
Nat Commun ; 13(1): 4302, 2022 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-35879305

RESUMO

The corpus cavernosum is the most important structure for penile erection, and its dysfunction causes many physiological and psychological problems. However, its cellular heterogeneity and signalling networks at the molecular level are poorly understood because of limited access to samples. Here, we profile 64,993 human cavernosal single-cell transcriptomes from three males with normal erection and five organic erectile dysfunction patients. Cell communication analysis reveals that cavernosal fibroblasts are central to the paracrine signalling network and regulate microenvironmental homeostasis. Combining with immunohistochemical staining, we reveal the cellular heterogeneity and describe a detailed spatial distribution map for each fibroblast, smooth muscle and endothelial subcluster in the corpus cavernosum. Furthermore, comparative analysis and related functional experiments identify candidate regulatory signalling pathways in the pathological process. Our study provides an insight into the human corpus cavernosum microenvironment and a reference for potential erectile dysfunction therapies.


Assuntos
Disfunção Erétil , Disfunção Erétil/genética , Humanos , Masculino , Músculo Liso/patologia , Ereção Peniana/fisiologia , Pênis , Transcriptoma/genética
15.
Theranostics ; 12(10): 4802-4817, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35832094

RESUMO

Background: Chemoresistance to 5-fluorouracil (5-FU) is a major barrier to influence the treatment efficiency of colorectal cancer (CRC) patients, while the precise molecular mechanisms underlying 5-FU resistance remain to be fully elucidated. Methods: The metabolic profiles including ATP generation, glucose consumption, lactate generation, and oxygen consumption rate (OCR) in 5-FU resistant CRC cells were compared with those in their parental cells. Subsequently, a series of in vitro and in vivo experiments were carried out to investigate the mechanisms responsible for metabolic reprogramming of 5-FU resistant CRC cells. Results: We found that 5-FU resistant CRC cells showed increased levels of ATP generation, glucose consumption, lactate generation, and OCR as compared with those in their parental cells. Further, increased levels of mRNA N6-methyladenosine (m6A) and methyltransferase-like 3 (METTL3) were observed in 5-FU resistant CRC cells. Inhibition or knockdown of METTL3 can suppress glycolysis and restore chemosensitivity of 5-FU resistant CRC cells. Mechanistically, METTL3 enhances the expression of LDHA, which catalyzes the conversion of pyruvate to lactate, to trigger glycolysis and 5-FU resistance. METTL3 can increase the transcription of LDHA via stabilizing mRNA of hypoxia-inducible factor (HIF-1α), further, METTL3 also triggers the translation of LDHA mRNA via methylation of its CDS region and recruitment of YTH domain-containing family protein 1 (YTHDF1). Targeted inhibition of METTL3/LDHA axis can significantly increase the in vitro and in vivo 5-FU sensitivity of CRC cells. Conclusion: Our study indicates that METTL3/LDHA axis-induced glucose metabolism is a potential therapy target to overcome 5-FU resistance in CRC cells.


Assuntos
Adenosina , Neoplasias Colorretais , Fluoruracila , L-Lactato Desidrogenase , Adenosina/análogos & derivados , Trifosfato de Adenosina/metabolismo , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Resistencia a Medicamentos Antineoplásicos , Fluoruracila/farmacologia , Glucose/metabolismo , Células HCT116 , Humanos , L-Lactato Desidrogenase/biossíntese , L-Lactato Desidrogenase/genética , L-Lactato Desidrogenase/metabolismo , Lactatos/metabolismo , Metiltransferases/genética , RNA Mensageiro
16.
Nat Commun ; 13(1): 3561, 2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35729175

RESUMO

Decoupling the electronic and geometric effects has been a long cherished goal for heterogeneous catalysis due to their tangled relationship. Here, a novel orthogonal decomposition method is firstly proposed to settle this issue in p-chloronitrobenzene hydrogenation reaction on size- and shape-controlled Pt nanoparticles (NPs) carried on various supports. Results suggest Fermi levels of catalysts can be modulated by supports with varied work function (Wf). And the selectivity on Pt NPs of similar size and shape is linearly related with the Wf of support. Optimized Fermi levels of the catalysts with large Wf weaken the ability of Pt NPs to fill valence electrons into the antibonding orbital of C-Cl bond, finally suppressing the hydrodehalogenation side reaction. Foremost, the geometric effect is firstly spun off through orthogonal relation based on series of linear relationships over various sizes of Pt NPs reflecting the electronic effect. Moreover, separable nested double coordinate system is established to quantitatively evaluate the two effects.

17.
Adv Sci (Weinh) ; 9(11): e2104636, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35152570

RESUMO

Constructing strong oxide-support interaction (SOSI) is compelling for modulating the atomic configurations and electronic structures of supported catalysts. Herein, ultrafine iridium oxide nanoclusters (≈1 nm) are anchored on vanadium oxide support (IrO2 /V2 O5 ) via SOSI. The as made catalyst, with a unique distorted IrO2 structure, is discovered to significantly boost the performance for pH-universal oxygen evolution reaction (OER). Based on experimental results and theoretical calculations, the distorted IrO2 active sites with flexible redox states in IrO2 /V2 O5 server as electrophilic centers balance the adsorption of oxo-intermediates and effectively facilitate the process of OO coupling, eventually propelling the fast turnover of water oxidation. As a result, IrO2 /V2 O5 demonstrates not only ultralow overpotentials at 10 mA cm-2 (266 mV, pH = 0; 329 mV, pH = 7; 283 mV, pH = 14) for OER, but also high-performance overall water electrolysis over a broad pH range, with a potential of mere 1.50 V (pH = 0), 1.65 V (pH = 7) or 1.49 V (pH = 14) at 10 mA cm-2 . In addition, SOSI can simultaneously secure the distorted active sites and thus remarkably improving the catalytic stability, making it a promising strategy to develop high-performance catalytic systems.

18.
Front Oncol ; 12: 1031160, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36644633

RESUMO

Background: Colorectal cancer is a common malignancy of the gastrointestinal tract, and its incidence and mortality rates have increased in recent years. RNF128 is an E3 ubiquitin ligase that plays an important role as a suppressor gene or oncogene in various cancers, but its mechanism in colorectal cancer is not yet clear. The aim of this study was to investigate the role and mechanism of RNF128 in colorectal cancer. Methods: The expression of RNF128 in colorectal cancer tissues was assessed by immunohistochemistry and western blotting. The proliferation ability of colorectal cancer cells was measured by colony formation assay and CCK-8 assay, the migration and invasion ability of colorectal cancer cells was measured by wound healing assay and transwell assay, and the protein expression levels of the Hippo signaling pathway and its target gene were examined by western blotting. Immunoprecipitation was used to assess the interaction of RNF128 with MST. In vivo, a xenograft tumor model was used to detect the effect of RNF128 on tumor growth. Results: At the tissue level, the expression level of RNF128 was significantly higher in colorectal cancer tissues than in adjacent normal tissues. In LoVo cells and HCT116 cells, the proliferation, migration and invasion abilities were significantly reduced with RNF128 knockdown. At the protein level, knockdown of RNF128 resulted in significant activation of the Hippo signaling pathway. In vivo experiments, the volume and weight of xenograft tumors in nude mice were significantly decreased compared with those in the normal control group with RNF128 knockdown. Conclusion: RNF128 promotes the malignant behaviors of colorectal cancer cells by inhibiting the Hippo signaling pathway, which may provide a new target for colorectal cancer prevention and treatment.

19.
ACS Appl Mater Interfaces ; 13(27): 31775-31784, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34227385

RESUMO

Selective hydrogenation of alkynes plays a pivotal role in the field of chemical production but still suffers from restrained catalytic activity and low alkene selectivity. Herein, a dynamic modification strategy was utilized by preferentially attaching diethylenetriamine (DETA) to the surface of the support to modify the Pd catalyst. The DETA-modified Pd catalyst demonstrates unprecedented reactivity (14,412 h-1) and selectivity as high as 94% for the semihydrogenation of 2-methyl-3-butyn-2-ol at 35 °C, presenting a 36-fold higher reactivity than the Lindlar catalyst. Moreover, the yield exceeds 98.2% at full conversion under no solvent and organic adsorbate conditions, indicating the potential applications for industrial production. Systematic studies reveal that flexible DETA serves in a reversible "breathing pattern" for the molecular discrimination by constructing dynamic metal-support interaction (DMSI), enabling selective exclusion of alkenes from the Pd surface. DETA is competent to dynamically adjust the adsorption behaviors of reactants and effectively boost the intrinsic activity of the modified catalyst. Impressively, the DETA-modified Pd catalyst exhibits exceptional stability even after being recycled 20 times. This work sheds light on a novel and applicable method for the rational design of heterogeneous catalysts via DMSI.

20.
Open Life Sci ; 16(1): 523-536, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34124372

RESUMO

Colorectal cancer (CRC) is the third most common malignancy worldwide. Circular RNAs (circRNAs) have been implicated in cancer biology. The purpose of the current work is to investigate the precise parts of circRNA centrosome and spindle pole-associated protein 1 (circ-CSPP1) in the progression of CRC. Our data showed that circ-CSPP1 was significantly overexpressed in CRC tissues and cells. The knockdown of circ-CSPP1 attenuated cell proliferation, migration, invasion and promoted apoptosis in vitro and weakened tumor growth in vivo. circ-CSPP1 directly targeted miR-431, and circ-CSPP1 knockdown modulated CRC cell progression in vitro via upregulating miR-431. Moreover, LIM and SH3 protein 1 (LASP1) was a functional target of miR-431 in modulating CRC cell malignant progression. Furthermore, circ-CSPP1 in CRC cells functioned as a posttranscriptional regulator on LASP1 expression by targeting miR-431. Our present study identified the oncogenic role of circ-CSPP1 in CRC partially by the modulation of the miR-431/LASP1 axis, providing evidence for circ-CSPP1 as a promising biomarker for CRC management.

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