Selective hydrogenation is an important industrial catalytic process in chemical upgrading, where Pd-based catalysts are widely used because of their high hydrogenation activities. However, poor ...selectivity and short catalyst lifetime because of heavy coke formation have been major concerns. In this work, atomically dispersed Pd atoms were successfully synthesized on graphitic carbon nitride （g-C3N4） using atomic layer deposition. Aberration-corrected high-angle annular dark-field scanning transmission electron microscopy （HAADF-STEM） confirmed the dominant presence of isolated Pd atoms without Pd nanoparticle （NP） formation. During selective hydrogenation of acetylene in excess ethylene, the g-C3N4-supported Pd NP catalysts had strikingly higher ethylene selectivities than the conventional Pd/Al2O3 and Pd/SiO2 catalysts. In-situ X-ray photoemission spectroscopy revealed that the considerable charge transfer from the Pd NPs to g-C3N4 likely plays an important role in the catalytic performance enhancement. More impressively, the single-atom Pd1/C3N4 catalyst exhibited both higher ethylene selectivity and higher coking resistance. Our work demonstrates that the single-atom Pd catalyst is a promising candidate for improving both selectivity and coking-resistance in hydrogenation reactions.
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•Pd1 SAC exhibits expressively high butenes selectivity.•Hydrogenation reactions follows the pseudo Horiuti-Polanyi mechanism.•1,3-butadiene adsorbs on Pd1 in a mono-π mode, distinct ...from that on Pd bulk.•The proximity O atom is found to be crucial for facilitating H2 dissociation.
Supported metal single-atom catalysts (SACs) with maximized metal atom efficiency and unique catalytic properties have drawn tremendous attention in the catalysis field. In this work, we reported that in selective hydrogenation of 1,3-butadiene, graphene supported Pd1 single atoms, synthesized by atomic layer deposition, exhibited expressively 100% butenes selectivity at 100% conversion at near ambient temperature, regardless of hydrogen partial pressures. The hydrogen reaction order was found to be about 1.2, indicating that hydrogenation dissociation is the rate-determining step. Combining with other structural characterization techniques, in situ X-ray absorption fine structure spectroscopy suggests that the Pd1 single atom likely bonds to the graphene support through three PdC and one PdOC coordinations. Density functional theory calculations show that 1,3-butadiene adsorbs on Pd1 via a mono-π adsorption mode (−0.98 eV), much stronger than that of H2 (−0.30 eV), which makes Pd1 to be predominantly covered with a 1,3-butadiene molecule during reaction, consistent very well with the results of H-D exchange reaction. Facilitated by the bridging O atom in the PdOC coordination, H2 dissociates at the 1,3-butadiene covered Pd1 atom in the heterolytic way, then hydrogenates the adsorbed 1,3-butadiene molecule by following the pseudo Horiuti-Polanyi mechanism. Distinct from its adsorption on extended Pd surfaces, such mono-π adsorption of 1,3-butadiene on Pd1 favors 1-butene formation, but impedes the secondary hydrogenation to butane owing to intensified steric hindrance, thus yielding the expressively high butenes selectivity over Pd1 SAC. These findings pave a new way to rational design SACs catalyst in selective hydrogenation reactions.
Liver metastasis is a major cause of colorectal cancer‐related death. Although DNase I displays antimetastatic activity by inhibition of NETs, its clinical use is limited due to its short biologic ...half‐life. AAV‐mediated gene expression of DNase I is a novel therapeutic strategy that could reduce the development of liver metastases through modulation of innate and adaptive tumor immunity.
Liver metastasis is the main cause of colorectal cancer (CRC)‐related death. Neutrophil extracellular traps (NETs) play important roles in CRC progression. Deoxyribonuclease I (DNase I) has been shown to alter NET function by cleaving DNA strands comprising the NET backbone. Moreover, DNase I displays high antimetastatic activity in multiple tumor models. To circumvent long‐term daily administrations of recombinant DNase I, we have developed an adeno‐associated virus (AAV) gene therapy vector to specifically express DNase I in the liver. In this study, we demonstrate AAV‐mediated DNase I liver gene transfer following a single intravenous injection suppresses the development of liver metastases in a mouse model of CRC liver metastasis. Increased levels of neutrophils and NET formation in tumors are associated with poor prognosis in many patients with advanced cancers. Neutrophil infiltration and NET formation were inhibited in tumor tissues with AAV‐DNase I treatment. This approach restored local immune responses at the tumor site by increasing the percentage of CD8+ T cells while keeping CD4+ T cells similar between AAV‐DNase I and AAV‐null treatments. Our data suggest that AAV‐mediated DNase I liver gene transfer is a safe and effective modality to inhibit metastasis and represents a novel therapeutic strategy for CRC.
Chemokines are a group of low molecular weight peptides. Their major function is the recruitment of leukocytes to inflammation sites, but they also play a key role in tumor growth, angiogenesis, and ...metastasis. In the last few years, accumulated experimental evidence supports that monokine induced by interferon (IFN)‐gamma (CXCL9), a member of CXC chemokine family and known to attract CXCR3‐ (CXCR3‐A and CXCR3‐B) T lymphocytes, is involved in the pathogenesis of a variety of physiologic diseases during their initiation and their maintenance. This review for the first time presents the most comprehensive summary for the role of CXCL9 in different types of tumors, and demonstrates its contradictory role of CXCL9 in tumor progression. Altogether, this is a useful resource for researchers investigating therapeutic opportunities for cancer.
This review for the first time presents the most comprehensive summarization of the role of CXCL9 in many types of tumor, and demonstrates the contradictory role of CXCL9 in tumor progression, which could be a useful resource providing rationale and support for future therapeutic opportunities for cancer.
Hepatocellular carcinoma (HCC) is a typical inflammation‐induced cancer and displays a complex interaction between the tumor microenvironment and tumor development. Immune cells in the HCC ...microenvironment play both pro‐ and anti‐tumoral roles in HCC progression. An increasing number of findings indicate that metabolic reprogramming is essential for immune cell differentiation and function. In this review, we discuss the metabolic changes of different immune cells and correlate these findings to HCC progression.
Immune cells in the Hepatocellular carcinoma (HCC) microenvironment play both pro‐and anti‐tumoral roles in HCC progression. An increasing number of findings indicate that metabolic reprogramming is essential for immune cell differentiation and function. In this review, we discuss the metabolic changes of different immune cells and correlate these findings to HCC progression.
Due to the specialization of tennis technical training, the teaching focus of tennis teaching has gradually shifted to the psychological skills training of tennis players. This work addresses the ...impact of psychological factors on tennis players' insufficient concentration in teaching and training on match results. It discusses the psychological changes' influencing factors in tennis training strategies and analyzes the current psychological changes that are easy to occur in tennis teaching. The Recurrent Neural Network (RNN) can simulate the human brain's information processing and learning process to establish models to study human psychological changes. To explore the influence of psychological changes on tennis training, artificial intelligence technology is combined to optimize the performance of RNN, and a prediction model of psychological distress in tennis training is constructed. Additionally, a questionnaire is applied to compare the sports state of tennis players before and after the psychological regulation intervention. The findings demonstrate that following psychological regulation, 73 % of players perform as usual, 20 % present exceptionally well, and 7 % do not perform as well as usual. These results indicate an improvement compared to previous performances, highlighting the efficacy of psychological regulation supported by optimized RNN under AI assistance. This study aims to foster a consistently positive psychological state among tennis players during daily training and competitions, ensuring that their competitive performance levels remain normal or even exceed their usual standards.
Immune checkpoint inhibitors can improve the prognosis of patients with advanced malignancy; however, only a small subset of advanced colorectal cancer patients in microsatellite-instability-high or ...mismatch-repair-deficient colorectal cancer can benefit from immunotherapy. Unfortunately, the mechanism behind this ineffectiveness is unclear. The tumor microenvironment plays a critical role in cancer immunity, and may contribute to the inhibition of immune checkpoint inhibitors and other novel immunotherapies in patients with advanced cancer. Herein, we demonstrate that the DNase I enzyme plays a pivotal role in the degradation of NETs, significantly dampening the resistance to anti-PD-1 blockade in a mouse colorectal cancer model by attenuating tumor growth. Remarkably, DNase I decreases tumor-associated neutrophils and the formation of MC38 tumor cell-induced neutrophil extracellular trap formation in vivo. Mechanistically, the inhibition of neutrophil extracellular traps with DNase I results in the reversal of anti-PD-1 blockade resistance through increasing CD8+ T cell infiltration and cytotoxicity. These findings signify a novel approach to targeting the tumor microenvironment using DNase I alone or in combination with immune checkpoint inhibitors.
Background
Special AT‐rich binding protein‐1 (SATB1) reprograms chromatin organization and transcription profiles to promote tumour growth and metastasis.
Aims
This study aimed to confirm the effects ...of SATB1 on the growth and metastasis of liver cancer and its specific regulation mechanism.
Methods
SATB1 expression was evaluated in human hepatoma tissue, adjacent noncancerous tissue and seven kinds of liver cancer cell lines. Cell cycle, cell proliferation, apoptosis and eptithelial‐mesenchymal transition (EMT) was investigated after enhanced or silenced expression of SATB1. The regulatory action of SATB1 on the expression of genes that are known to regulate cell cycle progression, apoptosis and EMT and the specific apoptotic pathway on which it acts were further analysed. Nude mice that received subcutaneous implantation were used to study the effects of SATB1 on tumour growth in vivo.
Results
Our data show that the high expression of SATB1 was observed in the human hepatocellular carcinoma tissue (26/45) and liver cancer cell lines with high metastatic potential. SATB1 upregulated CDK4 and downregulated p16
INK
4A to promote cell cycle progression and cell proliferation and prevented apoptosis by inhibiting the FADD–caspase‐8–caspase‐3 death receptor‐mediated apoptosis pathway. SATB1 also induced EMT concomitant with increased expression of Snail1, Slug, Twist and vimentin and decreased expression of E‐cadherin, tight junction protein ZO‐1 and desmoplakin. SATB1 promoted the growth of tumour in vivo.
Conclusion
These data suggest that the SATB1 gene may play an important role in the development and progression of liver cancer by regulation of genes related to cell cycle progression, apoptosis and EMT.
Metastasis of liver cancer is closely linked to tumor microenvironment, in which chemokines and their receptors act in an important role. The CXCR3, the receptor of chemokine CXCL9, belongs to a ...superfamily of rhodopsin-like seven transmembrane GPCRs and CXCR subfamily. In HCC tissues, CXCR3 was frequently upregulated and correlated with tumor size, tumor differentiation, portal invasion and metastasis. In the study, CXCR3-A isoform that was bound by CXCL9 was found to cause significant change of ERK1/2 phosphorylation level in the MAPK signaling pathway, consequently upregulating the MMP2 and MMP9 expression and promoting invasion and metastasis of CD133+ liver cancer cells. Also, CXCR3-A suppressed the adhesion ability of CD133+ liver cancer cells that stimulated by CXCL9 for 24h. These findings suggest that CXCR3 and its ligand CXCL9 could promote the metastasis of liver cancer cells and might be a potential target for the intervention of liver cancer metastasis.
Objectives
To develop a deep learning model combining CT scans and clinical information to predict overall survival in advanced hepatocellular carcinoma (HCC).
Methods
This retrospective study ...included immunotherapy-treated advanced HCC patients from 52 multi-national in-house centers between 2018 and 2022. A multi-modal prognostic model using baseline and the first follow-up CT images and 7 clinical variables was proposed. A convolutional-recurrent neural network (CRNN) was developed to extract spatial-temporal information from automatically selected representative 2D CT slices to provide a radiological score, then fused with a Cox-based clinical score to provide the survival risk. The model’s effectiveness was assessed using a time-dependent area under the receiver operating curve (AUC), and risk group stratification using the log-rank test. Prognostic performances of multi-modal inputs were compared to models of missing modality, and the size-based RECIST criteria.
Results
Two-hundred seven patients (mean age, 61 years ± 12 SD, 180 men) were included. The multi-modal CRNN model reached the AUC of 0.777 and 0.704 of 1-year overall survival predictions in the validation and test sets. The model achieved significant risk stratification in validation (hazard ratio HR = 3.330,
p
= 0.008), and test sets (HR = 2.024,
p
= 0.047) based on the median risk score of the training set. Models with missing modalities (the single-modal imaging-based model and the model incorporating only baseline scans) can still achieve favorable risk stratification performance (all
p
< 0.05, except for one,
p
= 0.053). Moreover, results proved the superiority of the deep learning-based model to the RECIST criteria.
Conclusion
Deep learning analysis of CT scans and clinical data can offer significant prognostic insights for patients with advanced HCC.
Critical relevance statement
The established model can help monitor patients’ disease statuses and identify those with poor prognosis at the time of first follow-up, helping clinicians make informed treatment decisions, as well as early and timely interventions.
Key Points
An AI-based prognostic model was developed for advanced HCC using multi-national patients.
The model extracts spatial-temporal information from CT scans and integrates it with clinical variables to prognosticate.
The model demonstrated superior prognostic ability compared to the conventional size-based RECIST method.
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