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1.
J Gastrointest Oncol ; 15(2): 710-720, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38756643

ABSTRACT

Background: Transarterial chemoembolization (TACE) is a non-radical treatment. How to improve the local response rate of tumor is the direction we have been exploring. The purpose of this study is to compare the efficacy and safety of occlusion-TACE (O-TACE) versus conventional TACE (C-TACE) in the treatment of patients with early to mid-stage hepatocellular carcinoma (HCC) of lesions being confined to the same hepatic venous drainage area. Methods: In this study, 40 patients with HCC were prospectively enrolled and randomly assigned to the O-TACE and C-TACE groups, and the efficacy of all patients was assessed at 1, 2, and 3 months after the first treatment, and adverse events (AEs) occurring during the treatment period were also recorded. Results: At 1, 2 and 3 months after the first treatment, patients in the O-TACE group had significantly better complete response (CR) rates (35% vs. 5%, P=0.04; 50% vs. 15%, P=0.04; 70% vs. 30%, P=0.02) than those in the C-TACE group. The most common AE was abdominal pain, and the liver function indexes of patients in both groups returned to the baseline level at 1 month after the first treatment, and there was no statistically significant difference in the rate of AEs between the two groups. Conclusions: O-TACE has a better CR rate and a favorable safety profile in patients with early to mid-stage HCC of lesions being confined to the same hepatic venous drainage area.

2.
BMC Genomics ; 25(1): 500, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38773374

ABSTRACT

BACKGROUND: The ricefield eel Monopterus albus undergoes a natural sex change from female to male during its life cycle, and previous studies have shown the potential mechanisms of this transition at the transcriptional and protein levels. However, the changes in protein levels have not been fully explored, especially in the intersexual stage. RESULTS: In the present study, the protein expression patterns in the gonadal tissues from five different periods, the ovary (OV), early intersexual stage gonad (IE), middle intersexual stage gonad (IM), late intersexual stage gonad (IL), and testis (TE), were determined by untargeted proteomics sequencing. A total of 5125 proteins and 394 differentially expressed proteins (DEPs) were detected in the gonadal tissues. Of the 394 DEPs, there were 136 between the OV and IE groups, 20 between the IM and IE groups, 179 between the IL and IM groups, and 59 between the TE and IL groups. Three candidate proteins, insulin-like growth factor 2 mRNA-binding protein 3 isoform X1 (Igf2bp3), triosephosphate isomerase (Tpi), and Cu-Zn superoxide dismutase isoform X1 [(Cu-Zn) Sod1], were validated by western blotting to verify the reliability of the data. Furthermore, metal metabolite-related proteins were enriched in the IL vs. IM groups and TE vs. IL groups, which had close relationships with sex change, including Cu2+-, Ca2+-, Zn2+- and Fe2+/Fe3+-related proteins. Analysis of the combined transcriptome data revealed consistent protein/mRNA expression trends for two metal metabolite-related proteins/genes [LOC109953912 and calcium Binding Protein 39 Like (cab39l)]. Notably, we detected significantly higher levels of Cu2+ during the sex change process, suggesting that Cu2+ is a male-related metal metabolite that may have an important function in male reproductive development. CONCLUSIONS: In summary, we analyzed the protein profiles of ricefield eel gonadal tissues in five sexual stages (OV, IE, IM, IL, and TE) and verified the plausibility of the data. After preforming the functional enrichment of metal metabolite-related DEPs, we detected the contents of the metal metabolites Zn2+, Cu2+, Ca2+, and Fe2+/Fe3+ at these five stages and screened for (Cu-Zn) Sod1 and Mmp-9 as possible key proteins in the sex reversal process.


Subject(s)
Metals , Animals , Male , Female , Metals/metabolism , Eels/metabolism , Eels/genetics , Proteomics , Fish Proteins/metabolism , Fish Proteins/genetics , Smegmamorpha/metabolism , Smegmamorpha/genetics , Hermaphroditic Organisms/metabolism , Hermaphroditic Organisms/genetics , Gene Expression Profiling , Testis/metabolism
3.
Phytomedicine ; 129: 155690, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38761523

ABSTRACT

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common pathological type of lung cancer. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been administered as the first-line therapy for patients with EGFR mutations in LUAD, but it is almost inevitable that resistance to EGFR-TKIs therapy eventually arises. Polyphyllin I (PPI), derived from Paris polyphylla rhizomes, has been shown to have potent anti-cancer properties in a range of human cancer types including LUAD. However, the role of PPI in gefitinib resistance and the underlying mechanism remain elusive. PURPOSE: To evaluate the antitumor impacts of PPI on gefitinib resistance cells and investigate its molecular mechanism. METHODS: CCK-8, wound healing, transwell assay, and xenograft model were performed to determine the anti-cancer effects of PPI as well as its ability to overcome gefitinib resistance. Immunoblotting, co-immunoprecipitation, phospho-RTK antibody array, qRT-PCR, and immunofluorescence were utilized to explore the mechanism by which PPI overrides gefitinib resistance. RESULTS: PPI inhibited cell survival, growth, and migration/invasion in both gefitinib-sensitive (PC9) and -resistant (PC9/GR) LUAD cells (IC50 at 2.0 µM). Significantly, treatment with PPI at 1.0 µM resensitized the resistant cells to gefitinib. Moreover, cell-derived xenograft experiments revealed that the combination of PPI and gefitinib overcame gefitinib resistance. The phospho-RTK array and immunoblotting analyses showed PPI significant inhibition of the VEGFR2/p38 pathway. In addition, molecular docking suggested the interaction between PPI and HIF-1α. Mechanistically, PPI reduced the protein expression of HIF-1α in both normoxia and hypoxia conditions by triggering HIF-1α degradation. Moreover, HIF-1α protein but not mRNA level was elevated in gefitinib-resistant LUAD. We further demonstrated that PPI considerably facilitated the binding of HIF-1α to VHL. CONCLUSIONS: We present a novel discovery demonstrating that PPI effectively counteracts gefitinib resistance in LUAD by modulating the VEGF/VEGFR2/p38 pathway. Mechanistic investigations unveil that PPI facilitates the formation of the HIF-1α /VHL complex, leading to the degradation of HIF-1α and subsequent inhibition of angiogenesis. These findings uncover a previously unidentified mechanism governing HIF-1α expression in reaction to PPI, providing a promising method for therapeutic interventions targeting EGFR-TKI resistance in LUAD.


Subject(s)
Adenocarcinoma of Lung , Diosgenin , Drug Resistance, Neoplasm , Gefitinib , Hypoxia-Inducible Factor 1, alpha Subunit , Lung Neoplasms , Mice, Nude , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factor Receptor-2 , Gefitinib/pharmacology , Humans , Drug Resistance, Neoplasm/drug effects , Vascular Endothelial Growth Factor Receptor-2/metabolism , Diosgenin/pharmacology , Diosgenin/analogs & derivatives , Lung Neoplasms/drug therapy , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Animals , Cell Line, Tumor , Adenocarcinoma of Lung/drug therapy , Vascular Endothelial Growth Factor A/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism , Mice , Mice, Inbred BALB C , Signal Transduction/drug effects , Xenograft Model Antitumor Assays , Female
4.
MRS Bull ; 49(4): 299-309, 2024.
Article in English | MEDLINE | ID: mdl-38645611

ABSTRACT

Abstract: The current work presents a novel flexible multifunctional platform for biological interface applications. The use of titania nanotube arrays (TNAs) as a multifunctional material is explored for soft-tissue interface applications. In vitro biocompatibility of TNAs to brain-derived cells was first examined by culturing microglia cells-the resident immune cells of the central nervous system on the surface of TNAs. The release profile of an anti-inflammatory drug, dexamethasone from TNAs-on-polyimide substrates, was then evaluated under different bending modes. Flexible TNAs-on-polyimide sustained a linear release of anti-inflammatory dexamethasone up to ~11 days under different bending conditions. Finally, microfabrication processes for patterning and transferring TNA microsegments were developed to facilitate structural stability during device flexing and to expand the set of compatible polymer substrates. The techniques developed in this study can be applied to integrate TNAs or other similar nanoporous inorganic films onto various polymer substrates. Impact statement: Titania nanotube arrays (TNAs) are highly tunable and biocompatible structures that lend themselves to multifunctional implementation in implanted devices. A particularly important aspect of titania nanotubes is their ability to serve as nano-reservoirs for drugs or other therapeutic agents that slowly release after implantation. To date, TNAs have been used to promote integration with rigid, dense tissues for dental and orthopedic applications. This work aims to expand the implant applications that can benefit from TNAs by integrating them onto soft polymer substrates, thereby promoting compatibility with soft tissues. The successful direct growth and integration of TNAs on polymer substrates mark a critical step toward developing mechanically compliant implantable systems with drug delivery from nanostructured inorganic functional materials. Diffusion-driven release kinetics and the high drug-loading efficiency of TNAs offer tremendous potential for sustained drug delivery for scientific investigations, to treat injury and disease, and to promote device integration with biological tissues. This work opens new opportunities for developing novel and more effective implanted devices that can significantly improve patient outcomes and quality of life. Supplementary information: The online version contains supplementary material available at 10.1557/s43577-023-00628-y.

5.
Ecotoxicol Environ Saf ; 276: 116308, 2024 May.
Article in English | MEDLINE | ID: mdl-38593496

ABSTRACT

BACKGROUND: Impact of outdoor and household air pollution on physical function remains unelucidated. This study examined the influence of various ambient particulate sizes (PM1, PM2.5, and PM10) and household fuel usage on physical function. METHODS: Data from the China Health and Retirement Longitudinal Study (CHARLS) spanning 2011 and 2015 were utilized. The physical functional score was computed by summing scores from four tests: grip strength, gait speed, chair stand test, and balance. Multivariate linear and linear mixed-effects models were used to explore the separate and combined effects of PM1, PM2.5, PM10 and household fuel use on physical function in the cross-sectional and longitudinal analyses, respectively, and to further observe the effects of fuel cleanup on physical function in the context of air pollution exposure. RESULTS: Both cross-sectional and longitudinal analyses revealed negative correlations between PM1 (ß = -0.044; 95% CI: -0.084, -0.004), PM2.5 (ß = -0.024; 95% CI: -0.046, -0.001), PM10 (ß = -0.041; 95% CI: -0.054, -0.029), and physical function, with a more pronounced impact observed for fine particulate matter (PM1). Cleaner fuel use was associated with enhanced physical function compared to solid fuels (ß = 0.143; 95% CI: 0.070, 0.216). The presence of air pollutants and use of solid fuels had a negative impact on physical function, while cleaner fuel usage mitigated the adverse effects of air pollutants, particularly in areas with high exposure. CONCLUSION: This study underscores the singular and combined detrimental effects of air pollutants and solid fuel usage on physical function. Addressing fine particulate matter, specifically PM1, and prioritizing efforts to improve household fuel cleanliness in regions with elevated air pollution levels are crucial for preventing physical disability.


Subject(s)
Air Pollutants , Air Pollution, Indoor , Particulate Matter , Particulate Matter/analysis , China , Humans , Cross-Sectional Studies , Longitudinal Studies , Middle Aged , Male , Air Pollutants/analysis , Air Pollution, Indoor/analysis , Air Pollution, Indoor/adverse effects , Female , Aged , Cohort Studies , Particle Size , Environmental Exposure , Cooking , Air Pollution/statistics & numerical data , Air Pollution/adverse effects
6.
Angew Chem Int Ed Engl ; : e202406535, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38652809

ABSTRACT

Borophenes have sparked considerable interest owing to their fascinating physical characteristics and diverse polymorphism. However, borophene nanoribbons (BNRs) with widths less than 2 nm have not been achieved. Herein, we report the experimental realization of supernarrow BNRs. Combining scanning tunneling microscopy imaging with density functional theory modeling and ab initio molecular dynamics simulations, we demonstrate that, under the applied growth conditions, boron atoms can penetrate the outermost layer of Au(111) and form BNRs composed of a pair of zigzag (2,2) boron rows. The BNRs have a width self-contained to ∼1 nm and dipoles at the edges to keep them separated. They are embedded in the outermost Au layer and shielded on top by the evacuated Au atoms, free of the need for post-passivation. Scanning tunneling spectroscopy reveals distinct edge states, primarily attributed to the localized spin at the BNRs' zigzag edges. This work adds a new member to the boron material family and introduces a new physical feature to borophenes.

7.
Biomed Mater ; 19(3)2024 May 03.
Article in English | MEDLINE | ID: mdl-38657629

ABSTRACT

Anodized titania nanotubes have been considered as an effective coating for bone implants due to their ability to induce osteogenesis, whereas the osteogenic mechanism is not fully understood. Our previous study has revealed the potential role of autophagy in osteogenic regulation of nanotubular surface, whereas how the autophagy is activated remains unknown. In this study, we focused on the cell membrane curvature-sensing protein Bif-1 and its effect on the regulation of autophagy. Both autophagosomes formation and autophagic flux were enhanced on the nanotubular surface, as indicated by LC3-II accumulation and p62 degradation. In the meanwhile, the Bif-1 was significantly upregulated, which contributed to autophagy activation and osteogenic differentiation through Beclin-1/PIK3C3 signaling pathway. In conclusion, these findings have bridged the gap between extracellular physical nanotopography and intracellular autophagy activation, which may provide a deeper insight into the signaling transition from mechanical to biological across the cell membrane.


Subject(s)
Autophagy , Beclin-1 , Cell Differentiation , Cell Membrane , Osteogenesis , Signal Transduction , Surface Properties , Animals , Cell Membrane/metabolism , Mice , Beclin-1/metabolism , Titanium/chemistry , Nanotubes/chemistry , Adaptor Proteins, Signal Transducing/metabolism , Humans , Osteoblasts/cytology , Osteoblasts/metabolism , Cell Line
8.
Adv Healthc Mater ; : e2400257, 2024 Mar 23.
Article in English | MEDLINE | ID: mdl-38520188

ABSTRACT

As newly discovered substrate anchored extracellular vesicles, migrasomes (Migs) may bring a new opportunity for manipulating target cells bioactivities. In this study, the M2 macrophages derived Migs are obtained by titania nanotubes surface (NTs). Due to the benefits of nanostructuring, the NTs surface is not only able to induce RAW264.7 for M2 polarization but also to generate more Migs formation, which can be internalized by following seeded mesenchymal stem cells (MSCs). Then, the NTs surface induced Migs are collected by density-gradient centrifugation for MSCs treatment. As indicated by immunofluorescence staining, alkaline phosphatase activity, and alizarin red staining, the osteogenic differentiation capacity of MSCs is significantly enhanced by Migs treatment, in line with the dosage. By RNA-sequence analysis, the enhancement of osteogenic differentiation is correlated with PI3K-AKT pathway activation that may originate from the M2 polarization state of donor cells. Finally, the Migs are coated onto Ti surface for therapeutic application. Both the in vitro and in vivo analysis reveal that the Migs coated Ti implant shows significant enhancement of osteogenesis. In conclusion, this study suggests that the nanosurface may be a favorable platform for Migs production, which may bring a new concept for tissue regeneration.

9.
Bioinformatics ; 40(3)2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38429953

ABSTRACT

MOTIVATION: Promoters with desirable properties are crucial in biotechnological applications. Generative AI (GenAI) has demonstrated potential in creating novel synthetic promoters with significantly enhanced functionality. However, these methods' reliance on various programming frameworks and specific task-oriented contexts limits their flexibilities. Overcoming these limitations is essential for researchers to fully leverage the power of GenAI to design promoters for their tasks. RESULTS: Here, we introduce GPro (Generative AI-empowered toolkit for promoter design), a user-friendly toolkit that integrates a collection of cutting-edge GenAI-empowered approaches for promoter design. This toolkit provides a standardized pipeline covering essential promoter design processes, including training, optimization, and evaluation. Several detailed demos are provided to reproduce state-of-the-art promoter design pipelines. GPro's user-friendly interface makes it accessible to a wide range of users including non-AI experts. It also offers a variety of optional algorithms for each design process, and gives users the flexibility to compare methods and create customized pipelines. AVAILABILITY AND IMPLEMENTATION: GPro is released as an open-source software under the MIT license. The source code for GPro is available on GitHub for Linux, macOS, and Windows: https://github.com/WangLabTHU/GPro, and is available for download via Zenodo repository at https://zenodo.org/doi/10.5281/zenodo.10681733.


Subject(s)
Algorithms , Software , Promoter Regions, Genetic , Artificial Intelligence
10.
BMC Genomics ; 25(1): 145, 2024 Feb 06.
Article in English | MEDLINE | ID: mdl-38321406

ABSTRACT

BACKGROUND: Schizothorax o'connori is an endemic fish distributed in the upper and lower reaches of the Yarlung Zangbo River in China. It has experienced a fourth round of whole gene replication events and is a good model for exploring the genetic differentiation and environmental adaptability of fish in the Qinghai-Tibet Plateau. The uplift of the Qinghai-Tibet Plateau has led to changes in the river system, thereby affecting gene exchange and population differentiation between fish populations. With the release of fish whole genome data, whole genome resequencing has been widely used in genetic evolutionary analysis and screening of selected genes in fish, which can better elucidate the genetic basis and molecular environmental adaptation mechanisms of fish. Therefore, our purpose of this study was to understand the population structure and adaptive characteristics of S. o'connori using the whole-genome resequencing method. RESULTS: The results showed that 23,602,746 SNPs were identified from seven populations, mostly distributed on chromosomes 2 and 23. There was no significant genetic differentiation between the populations, and the genetic diversity was relatively low. However, the Zangga population could be separated from the Bomi, Linzhi, and Milin populations in the cluster analysis. Based on historical dynamics analysis of the population, the size of the ancestral population of S. o'connori was affected by the late accelerated uplift of the Qinghai Tibet Plateau and the Fourth Glacial Age. The selected sites were mostly enriched in pathways related to DNA repair and energy metabolism. CONCLUSION: Overall, the whole-genome resequencing analysis provides valuable insights into the population structure and adaptive characteristics of S. o'connori. There was no obvious genetic differentiation at the genome level between the S. o'connori populations upstream and downstream of the Yarlung Zangbo River. The current distribution pattern and genetic diversity are influenced by the late accelerated uplift of the Qinghai Tibet Plateau and the Fourth Ice Age. The selected sites of S. o'connori are enriched in the energy metabolism and DNA repair pathways to adapt to the low temperature and strong ultraviolet radiation environment at high altitude.


Subject(s)
Cyprinidae , Ultraviolet Rays , Animals , Tibet , China , Cyprinidae/genetics , Sequence Analysis, DNA
11.
Sensors (Basel) ; 24(2)2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38257517

ABSTRACT

Efficient geometric evaluation of roads and tunnels is crucial to traffic management, especially in post-disaster situations. This paper reports on a study of the geometric feature detection method based on multi-sensor mobile laser scanning (MLS) system data. A portable, low-cost system that can be mounted on vehicles and utilizes integrated laser scanning devices was developed. Coordinate systems and timestamps from numerous devices were merged to create 3D point clouds of objects being measured. Feature points reflecting the geometric information of measuring objects were retrieved based on changes in the point cloud's shape, which contributed to measuring the road width, vertical clearance, and tunnel cross section. Self-developed software was used to conduct the measuring procedure, and a real-time online visualized platform was designed to reconstruct 3D models of the measured objects, forming a 3D digital map carrying the obtained geometric information. Finally, a case study was carried out. The measurement results of several representative nodes are discussed here, verifying the robustness of the proposed system. In addition, the main sources of interference are also discussed.

12.
Cancer Immunol Immunother ; 73(1): 1, 2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38175202

ABSTRACT

BACKGROUND: Tumor-associated macrophages (TAMs) are the predominant immune cells in the tumor microenvironment and portend poor prognosis. However, the molecular mechanisms underlying the tumor promotion of TAMs have not been fully elucidated. METHODS: Coculture of gastric cancer cells with U937 cells was performed to investigate the impact of TAMs on cancer cell behavior. MicroRNA (miRNA) microarray and bioinformatics were applied to identify the involved miRNAs and the functional target genes. The regulation of the miRNA on its target gene was studied using anti-miRNA and miRNA mimic. RESULTS: Coculture with CD204+ M2-like TAMs increased proliferation, migration, and epithelial-mesenchymal transition of gastric cancer cells. MiR-210 was the most upregulated miRNA in cancer cells identified by miRNA microarray after coculture. In gastric cancer tissues, miR-210 expression was positively correlated with CD204+ M2-like TAM infiltration. Inactivation of miR-210 by antimir attenuated CD204+ M2-like TAMs-induced cancer cell migration. Using pharmacological inhibitors and neutralizing antibodies, CD204+ M2-like TAMs-secreted TNFα was found to upregulate miR-210 through NF-κB/HIF-1α signaling. Bioinformatics analysis showed netrin-4 (NTN4) as a potential target of miR-210 to suppress gastric cancer cell migration. We also found an inverse expression between miR-210 and NTN4 in cancer cells after coculture or in tumor xenografts. Anti-miR-210 increased NTN4 expression, while miR-210 mimics downregulated NTN4 in cancer cells. Reporter luciferase assays showed that MiR-210 mimics suppressed NTN4 3' untranslated region-driven luciferase activity in cancer cells, but this effect was blocked after mutating miR-210 binding site. CONCLUSIONS: CD204+ M2-like TAMs can utilize the TNF-α/NF-κB/HIF-1α/miR-210/NTN4 pathway to facilitate gastric cancer progression.


Subject(s)
MicroRNAs , Stomach Neoplasms , Humans , Stomach Neoplasms/genetics , NF-kappa B , Tumor-Associated Macrophages , MicroRNAs/genetics , Luciferases , Tumor Microenvironment , Netrins
13.
J Exp Bot ; 75(5): 1633-1646, 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38180121

ABSTRACT

The petals of ornamental plants such as roses (Rosa spp.) are the most economically important organs. This delicate, short-lived plant tissue is highly susceptible to pathogens, in large part because the walls of petal cells are typically thinner and more flexible compared with leaf cells, allowing the petals to fold and bend without breaking. The cell wall is a dynamic structure that rapidly alters its composition in response to pathogen infection, thereby reinforcing its stability and boosting plant resistance against diseases. However, little is known about how dynamic changes in the cell wall contribute to resistance to Botrytis cinerea in rose petals. Here, we show that the B. cinerea-induced transcription factor RhbZIP17 is required for the defense response of rose petals. RhbZIP17 is associated with phenylpropanoid biosynthesis and binds to the promoter of the lignin biosynthesis gene RhCAD1, activating its expression. Lignin content showed a significant increase under gray mold infection compared with the control. RhCAD1 functions in the metabolic regulation of lignin production and, consequently, disease resistance, as revealed by transient silencing and overexpression in rose petals. The WRKY transcription factor RhWRKY30 is also required to activate RhCAD1 expression and enhance resistance against B. cinerea. We propose that RhbZIP17 and RhWRKY30 increase lignin biosynthesis, improve the resistance of rose petals to B. cinerea, and regulate RhCAD1 expression.


Subject(s)
Rosa , Transcription Factors , Transcription Factors/genetics , Transcription Factors/metabolism , Rosa/genetics , Lignin/metabolism , Gene Expression Regulation , Botrytis/physiology , Plant Diseases/genetics , Disease Resistance/genetics , Gene Expression Regulation, Plant
14.
Biomed Pharmacother ; 170: 116074, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38147732

ABSTRACT

Hepatocellular carcinoma (HCC) remains a major global health burden, and sorafenib, a multi-kinase inhibitor, has shown effectiveness in the treatment of HCC and is considered as the first-line therapy for advanced HCC. However, the response to sorafenib varies among patients, and the development of drug resistance poses a prevalent obstacle. Ferroptosis, a newly characterized form of cell death featured by iron-dependent lipid peroxidation, has emerged as a critical player in the reaction to sorafenib therapy in HCC. The induction of ferroptosis has been shown to augment the anticancer benefits of sorafenib. However, it has also been observed to contribute to sorafenib resistance. This review presents a comprehensive and thorough analysis that elucidates the intricate relationship between ferroptosis and sorafenib over recent years, aiming to formulate effective therapeutic approaches for liver cancer. Based on this exploration, we propose innovative strategies intended to overcome sorafenib resistance via targeted modulation of ferroptosis.


Subject(s)
Antineoplastic Agents , Carcinoma, Hepatocellular , Ferroptosis , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/pathology , Sorafenib/pharmacology , Sorafenib/therapeutic use , Liver Neoplasms/pathology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Cell Line, Tumor
15.
BMJ Open ; 13(12): e074837, 2023 12 21.
Article in English | MEDLINE | ID: mdl-38135333

ABSTRACT

INTRODUCTION: Perioperative rehabilitation (PORT) has shown a positive effect on patients undergoing cardiac surgery. However, there are minimal data on the impact of short-term PORT in cardiac surgery, which is associated with higher postoperative morbidity and mortality. The trial will assess the efficacy of short-term PORT in reducing in-hospital mortality, postoperative pulmonary complications and length of stay, compared with the usual care in cardiac surgical patients. METHODS AND ANALYSIS: This is a single-centre prospective, randomised, open, controlled trial with a 1:1 ratio. Consecutive 800 adult patients undergoing elective valve surgery will be randomised to either usual care or in-hospital short-term PORT that consists of education, inspiratory muscle training, active cycle of breathing techniques and early mobilisation. The primary outcome of this study will be a composite of in-hospital all-cause mortality, incidence of postoperative pulmonary complications and the ratio of postoperative hospitalisation >7 days. ETHICS AND DISSEMINATION: The PORT study was granted by the Medical Research Ethics Committee of Guangdong Provincial People's Hospital in August 2018. Findings will be disseminated to patients, clinicians and commissioning groups through peer-reviewed publication. TRIAL REGISTRATION NUMBER: NCT03709511.


Subject(s)
Cardiac Surgical Procedures , Postoperative Complications , Adult , Humans , Prospective Studies , Postoperative Complications/etiology , Cardiac Surgical Procedures/adverse effects , Heart , Elective Surgical Procedures , Randomized Controlled Trials as Topic
16.
Nat Commun ; 14(1): 6309, 2023 10 09.
Article in English | MEDLINE | ID: mdl-37813854

ABSTRACT

Designing promoters with desirable properties is essential in synthetic biology. Human experts are skilled at identifying strong explicit patterns in small samples, while deep learning models excel at detecting implicit weak patterns in large datasets. Biologists have described the sequence patterns of promoters via transcription factor binding sites (TFBSs). However, the flanking sequences of cis-regulatory elements, have long been overlooked and often arbitrarily decided in promoter design. To address this limitation, we introduce DeepSEED, an AI-aided framework that efficiently designs synthetic promoters by combining expert knowledge with deep learning techniques. DeepSEED has demonstrated success in improving the properties of Escherichia coli constitutive, IPTG-inducible, and mammalian cell doxycycline (Dox)-inducible promoters. Furthermore, our results show that DeepSEED captures the implicit features in flanking sequences, such as k-mer frequencies and DNA shape features, which are crucial for determining promoter properties.


Subject(s)
Escherichia coli , Regulatory Sequences, Nucleic Acid , Animals , Humans , Promoter Regions, Genetic/genetics , Escherichia coli/genetics , Escherichia coli/metabolism , Mammals/genetics
17.
Front Cardiovasc Med ; 10: 1263897, 2023.
Article in English | MEDLINE | ID: mdl-37771668

ABSTRACT

Due to structural abnormalities in the leaflets, patients with bicuspid aortic valve (BAV) may develop isolated aortic valve disease, such as aortic regurgitation, aortic stenosis, or a combination of both. In addition to valvular pathology, numerous studies have indicated that approximately 40% of BAV patients exhibit aortic pathologies characterized by aortic dilatation. According to guidelines for valvular diseases, patients with BAV who require surgical aortic valve replacement (SAVR) and have a diameter of the aortic sinuses or ascending aorta ≥4.5 cm are recommended to undergo concomitant replacement of the aortic sinuses or ascending aorta. However, we encountered a case in 2020 involving a patient with severe aortic regurgitation due to BAV and an ascending aortic diameter of 4.2 cm. This patient underwent SAVR and ascending aortoplasty surgery at our center. Remarkably, three years postoperatively, the patient's aortic diameter rapidly expanded by nearly threefold, which also suggests the risk of encountering a giant aortic root aneurysm during reoperation. Unfortunately, a fatal rupture of a giant aortic root aneurysm was encountered during re-sternotomy. Fortunately, with adequate preoperative planning, we successfully managed to avert this perilous situation. The patient recovered without complications and was discharged on the 8th day. Individualized surgical plans were formulated based on a comprehensive evaluation of the perioperative conditions.

18.
Quant Imaging Med Surg ; 13(9): 5877-5886, 2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37711799

ABSTRACT

Background: EAS index is reported to be an adjunctive tool for risk stratification in addition to left ventricular ejection fraction (LVEF). This study aimed to verify the predictive value of EAS index among coronary artery disease (CAD) patients with different cardiac systolic function levels. Methods: A total of 477 patients with obstructive CAD were included in the exploratory analysis of a prospective cohort between October 2017 and January 2018 at Guangdong Provincial People's Hospital. EAS index, e'/(a' × s'), is a novel parameter assessed by tissue Doppler imaging (TDI) indicating combined diastolic and systolic performance. Any occurrence of major adverse cardiovascular event (MACE) was recorded, including first onset of myocardial infarction, stroke, readmission for heart failure, coronary revascularization, or cardiovascular death that occurred within 6 months of the first admission. Kaplan-Meier survival and Cox regression analyses were applied to testify the predictive value of EAS index for cardiovascular outcome. Results: A total of 415 patients (87.2%) completed the follow-up (median, 25.9 months) and experienced 101 (24.3%) MACEs, 17 (4.0%) deaths, and 139 (33.4%) composite events. Elevated EAS index was significantly associated with a higher incidence of MACE, even after adjustment for age, sex, body mass index, N-terminal pro brain natriuretic peptide, high-sensitivity troponin T, high-density lipoprotein, stenosis degree, and other TDI parameters [Model 3, hazard ratio: 1.81, 95% confidence interval (CI): 1.15-2.85]. For different levels of cardiac function, Kaplan-Meier survival analysis revealed that elevated EAS index was associated with higher MACE incidence only in patients with LVEF ≥50% (P<0.05). Conclusions: EAS index is an independent predictor of MACE in patients with obstructive CAD, which could be utilized as a tool for risk stratification in CAD patients or incorporated into a prediction model to improve efficacy.

19.
Nucl Med Commun ; 44(12): 1144-1150, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-37706260

ABSTRACT

BACKGROUND: This study evaluated total-body glucose metabolism in a preclinical lab animal, the rabbit, by employing a dynamic glucose metabolic image obtained with total-body fluorine-18 fluorodeoxyglucose ( 18 F-FDG) PET/computed tomography (PET/CT). METHODS: The dynamic total-body PET/CT system was used to obtain glucose metabolic imaging from 10 sedated body-matched rabbits. The standard uptake value (SUV) of 18 F-FDG was used to evaluate glucose metabolism. In addition, the correlation between glucose metabolism and sexes was assessed, as well as metabolic differences between left- and right sides. RESULTS: We found significant distribution heterogeneity of glucose in several organs across the entire body. There were no significant metabolic differences between sexes and between bilateral sides in the 10 rabbits. Thereafter, we assayed the major organ SUV changes by dynamic PET/CT of the major organs. The heart, liver, and urinary system showed more 18 F-FDG, whereas the skeletal muscle, brain, spinal cord, and lungs incorporated less 18 F-FDG. The phenotype of 18 F-FDG uptake was highly correlated with the physiological functions. The 18 F-FDG accumulation in urinary system were observed which could reflect the renal parenchyma glucose metabolism indirectly. However, the low 18 F-FDG uptake in the brain and spinal cord was due to sedation. CONCLUSION: The total-body glucose metabolic atlas depicted with 18 F-FDG dynamic PET/CT may be used as a reference for assessing pathological 18 F-FDG uptake. Furthermore, this study could be a reference for preclinical research involving abnormality of glucose metabolism.


Subject(s)
Fluorodeoxyglucose F18 , Positron Emission Tomography Computed Tomography , Animals , Rabbits , Positron Emission Tomography Computed Tomography/methods , Positron-Emission Tomography , Tomography, X-Ray Computed , Glucose
20.
Front Mol Biosci ; 10: 1239952, 2023.
Article in English | MEDLINE | ID: mdl-37609372

ABSTRACT

DNA origami is a cutting-edge DNA self-assembly technique that neatly folds DNA strands and creates specific structures based on the complementary base pairing principle. These innovative DNA origami nanostructures provide numerous benefits, including lower biotoxicity, increased stability, and superior adaptability, making them an excellent choice for transporting anti-tumor agents. Furthermore, they can considerably reduce side effects and improve therapy success by offering precise, targeted, and multifunctional drug delivery system. This comprehensive review looks into the principles and design strategies of DNA origami, providing valuable insights into this technology's latest research achievements and development trends in the field of anti-tumor drug delivery. Additionally, we review the key function and major benefits of DNA origami in cancer treatment, some of these approaches also involve aspects related to DNA tetrahedra, aiming to provide novel ideas and effective solutions to address drug delivery challenges in cancer therapy.

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