ABSTRACT
Renal cell carcinoma (RCC) is considered radio- and chemo-resistant. Immune checkpoint inhibitors (ICIs) have demonstrated significant clinical efficacy in advanced RCC. However, the overall response rate of RCC to monotherapy remains limited. Given its immunomodulatory effects, a combination of radiotherapy (RT) with immunotherapy is increasingly used for cancer treatment. Heavy ion radiotherapy, specifically the carbon ion radiotherapy (CIRT), represents an innovative approach to cancer treatment, offering superior physical and biological effectiveness compared to conventional photon radiotherapy and exhibiting obvious advantages in cancer treatment. The combination of CIRT and immunotherapy showed robust effectiveness in preclinical studies of various tumors, thus holds promise for overcoming radiation resistance of RCC and enhancing therapeutic outcomes. Here, we provide a comprehensive review on the biophysical effects of CIRT, the efficacy of combination treatment and the underlying mechanisms involved in, as well as its therapeutic potential specifically within RCC.
Subject(s)
Carcinoma, Renal Cell , Heavy Ion Radiotherapy , Immune Checkpoint Inhibitors , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/therapy , Carcinoma, Renal Cell/radiotherapy , Carcinoma, Renal Cell/immunology , Immune Checkpoint Inhibitors/therapeutic use , Kidney Neoplasms/therapy , Kidney Neoplasms/radiotherapy , Kidney Neoplasms/immunology , Combined Modality Therapy , Animals , Immunotherapy/methodsABSTRACT
Renal cell carcinoma (RCC) ranks among the leading causes of cancer-related mortality. Despite extensive research, the precise etiology and progression of RCC remain incompletely elucidated. Long noncoding RNA (lncRNA) has been identified as competitive endogenous RNA (ceRNA) capable of binding to microRNA (miRNA) sites, thereby modulating the expression of messenger RNAs (mRNA) and target genes. This regulatory network is known to exert a pivotal influence on cancer initiation and progression. However, the specific role and functional significance of the lncRNA-miRNA-mRNA ceRNA network in RCC remain poorly understood. The RCC transcriptome data was obtained from the gene expression omnibus database. The identification of differentially expressed long noncoding RNAs (DElncRNAs), differentially expressed miRNAs, and differentially expressed mRNAs (DEmRNAs) between RCC and corresponding paracancer tissues was performed using the "Limma" package in R 4.3.1 software. We employed a weighted gene co-expression network analysis to identify the key DElncRNAs that are most relevant to RCC. Subsequently, we utilized the encyclopedia of RNA interactomes database to predict the interactions between these DElncRNAs and miRNAs, and the miRDB database to predict the interactions between miRNAs and mRNAs. Therefore, key DElncRNAs were obtained to verify the expression of their related genes in the The Cancer Genome Atlas database and to analyze the prognosis. The construction of RCC-specific lncRNA-miRNA-mRNA ceRNA network was carried out using Cytoscape 3.7.0. A total of 286 DElncRNAs, 56 differentially expressed miRNAs, and 2065 DEmRNAs were identified in RCC. Seven key DElncRNAs (GAS6 antisense RNA 1, myocardial infarction associated transcript, long intergenic nonprotein coding RNA 921, MMP25 antisense RNA 1, Chromosome 22 Open Reading Frame 34, MIR34A host gene, MIR4435-2 host gene) were identified using weighted gene co-expression network analysis and encyclopedia of RNA interactomes databases. Subsequently, a network diagram comprising 217 nodes and 463 edges was constructed based on these key DElncRNAs. The functional analysis of DEmRNAs in the ceRNA network was conducted using Kyoto Encyclopedia of Genes and Genomes and gene ontology. We constructed RCC-specific ceRNA networks and identified the crucial lncRNAs associated with RCC using bioinformatics analysis, which will help us further understand the pathogenesis of this disease.
Subject(s)
Carcinoma, Renal Cell , Gene Regulatory Networks , Kidney Neoplasms , MicroRNAs , RNA, Long Noncoding , RNA, Messenger , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Humans , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Kidney Neoplasms/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Gene Expression Regulation, Neoplastic , Databases, Genetic , Gene Expression Profiling/methods , RNA, Competitive EndogenousABSTRACT
Many studies have indicated that tumor growth factor-beta (TGF-ß) signaling mediates radiation-induced bystander effects (RIBEs). The primary cilium (PC) coordinates several signaling pathways including TGF-ß signaling to regulate diverse cellular processes. But whether the PC participates in TGF-ß induced RIBEs remains unclear. The cellular levels of TGF-ß1 were detected by western blot analysis and the secretion of TGF-ß1 was measured by ELISA kit. The ciliogenesis was altered by CytoD treatment, STIL siRNA transfection, IFT88 siRNA transfection, or KIF3a siRNA transfection, separately, and was detected by western blot analysis and immunofluorescence staining. G0 /G1 phase cells were arrested by serum starvation and S phase cells were induced by double thymidine block. The TGF-ß1 signaling was interfered by LY2109761, a TGF-ß receptor 1 (TßR1) inhibitor, or TGF-ß1 neutral antibody. The DNA damages were induced by TGF-ß1 or radiated conditional medium (RCM) from irradiated cells and were reflected by p21 expression, 53BP1 foci, and γH2AX foci. Compared with unirradiated control, both A549 and Beas-2B cells expressed and secreted more TGF-ß1 after carbon ion beam or X-ray irradiation. RCM collected from irradiated cells or TGF-ß1 treatment caused an increase of DNA damage in cocultured unirradiated Beas-2B cells while blockage of TGF-ß signaling by TßR1 inhibitor or TGF-ß1 neutral antibody alleviates this phenomenon. IFT88 siRNA or KIF3a siRNA impaired PC formation resulted in an aggravated DNA damage in bystander cells, while elevated PC formation by CytoD or STIL siRNA resulted in a decrease of DNA damage. Furthermore, TGF-ß1 induced more DNA damages in S phases cells which showed lower PC formation rate and less DNA damages in G0 /G1 phase cells which showed higher PC formation rate. This study demonstrates the particular role of primary cilia during RCM induced DNA damages through TGF-ß1 signaling restriction and thereby provides a functional link between primary cilia and RIBEs.
Subject(s)
Bystander Effect , Transforming Growth Factor beta1 , Bystander Effect/genetics , Bystander Effect/radiation effects , Cilia/metabolism , DNA , RNA, Small Interfering/genetics , Transforming Growth Factor beta/metabolism , Transforming Growth Factor beta1/metabolism , Humans , Cell Line, TumorABSTRACT
Selective electro-oxidation of aliphatic alcohols into value-added carboxylates at lower potentials than that of the oxygen evolution reaction (OER) is an environmentally and economically desirable anode reaction for clean energy storage and conversion technologies. However, it is challenging to achieve both high selectivity and high activity of the catalysts for the electro-oxidation of alcohols, such as the methanol oxidation reaction (MOR). Herein, a monolithic CuS@CuO/copper-foam electrode for the MOR with superior catalytic activity and almost 100% selectivity for formate is reported. In the core-shell CuS@CuO nanosheet arrays, the surface CuO directly catalyzes MOR, while the subsurface sulfide not only serves as an inhibitor to attenuate the oxidative power of the surface CuO to achieve selective oxidation of methanol to formate and prevent over-oxidation of formate to CO2 but also serves as an activator to form more surface O defects as active sites and enhances the methanol adsorption and charge transfer to achieve superior catalytic activity. CuS@CuO/copper-foam electrodes can be prepared on a large scale by electro-oxidation of copper-foam at ambient conditions and can be readily utilized in clean energy technologies.
ABSTRACT
H3K56 acetylation (H3K56Ac) was reported to play a critical role in chromatin assembly; thus, H3K56ac participates in the regulation of DNA replication, cell cycle progression, DNA repair, and transcriptional activation. To investigate the influence of DNA damage regulators on the acetylation of histone H3 and gene transcription, U2OS cells expressing SNAP-labeled H3.1 or SNAP-labeled H3.3 were treated with ATM, ATR, or a Chk1 inhibitor after ultraviolet (UV) radiation. The levels of H3.1K56ac, H3.3K56ac, and other H3 site-specific acetylation were checked at different time points until 24 h after UV radiation. The difference in gene transcription levels was also examined by mRNA sequencing. The results identified Chk1 as an important regulator of histone H3K56 acetylation in the restoration of both H3.1K56ac and H3.3K56ac. Moreover, compromising Chk1 activity via chemical inhibitors suppresses gene transcription after UV radiation. The study suggests a previously unknown role of Chk1 in regulating H3K56 and some other site-specific H3 acetylation and in reprograming gene transcription during DNA damage repair.
ABSTRACT
To mitigate environmental pollution caused by the escape of dust during coal storage and transportation, humic acid (HA) and grafted acrylamide (AM) were used as raw materials to prepare a composite dust suppressant suitable for coal storage and transportation. Single-factor experiments were used to explore the optimal synthesis conditions of the dust suppressant, and the microstructure of the product was studied using Fourier-transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (1H-NMR), scanning electron microscopy (SEM), and other methods. The wetting effect of the dust suppressant on coal was also investigated by way of molecular dynamics (MD) simulations. The experimental results showed that the dust suppressant had good wind erosion resistance (wind erosion rate 10.2%), shock resistance (loss rate 3.63%), and anti-evaporation performance, while the MD simulation and permeability analysis results showed that the dust suppressant had an excellent wetting effect on the coal surface. SEM images revealed that the dust suppressant can fill the gaps between coal dust particles and bond them together to form a consolidated layer, thereby effectively inhibiting the escape of dust sources during coal storage and transportation.
Subject(s)
Coal Mining , Coal , Coal/analysis , Dust/analysis , Humic Substances , WindABSTRACT
Conductive hydrogel-based epidermal sensors are attracting significant interest due to their great potential in soft robotics, electronic skins, bioelectronics and personalized healthcare monitoring. However, the conventional conductive hydrogel-based epidermal sensors cannot be degraded, resulting in the significant problem of waste, which will gradually increase the burden on the environment. Herein, degradable adhesive epidermal sensors were assembled using conductive nanocomposite hydrogels, which were prepared via the conformal coating of cellulose nanofiber (CNF) networks and supramolecular interaction among CNF, polydopamine (PDA), Fe3+, and polyacrylamide (PAM). They exhibited superior mechanical properties, reliable degradability (30 days in water), and excellent self-adhesiveness. The obtained hydrogels could be assembled as self-adhesive, degradable epidermal sensors for real-time human motion monitoring. Air could be sucked into the hydrogels during their swelling process, thereby oxidizing the tris-catechol-Fe3+ complexes and releasing Fe3+. Finally, the polymer networks were degraded via a Fenton-like reaction dominated by S2O82- and Fe(ii/iii) with the help of the catechol groups of PDA. This work paves the way for the potential fabrication of degradable, and self-adhesive epidermal sensors for applications in human-machine interactions, implantable bioelectronics, and personalized healthcare monitoring.
Subject(s)
Adhesives , Resin Cements , Electric Conductivity , Humans , Hydrogels , NanogelsABSTRACT
Novel gel materials are proposed for fire prevention and extinction in coal mines, where spontaneous combustion of coal continues to pose a significant risk. Cationic polyacrylamide (CPAM), anionic polyacrylamide (HPAM), and carboxymethyl cellulose (CMC) were each introduced separately into a sodium silicate (WG) gel, to obtain three gels labeled as CPAM/WG, HPAM/WG, and CMC/WG. A crosslinking agent, aluminum citrate, was subsequently added to the HPAM/WG and CMC/WG gels to afford two novel interpenetrating network hydrogels, HPAM-Al3+/WG and CMC-Al3+/WG, respectively. Among the various gels, the HPAM-Al3+/WG hydrogel exhibits the best seepage capacity, water retention capacity, compressive strength, and inhibition characteristics, which effectively resolve the post-water-loss cracking and pulverization problems commonly associated with inorganic consolidated silica gels. The microstructures of all the gels were investigated by scanning electron microscopy and their inhibitory effects on the oxidation of hydroxyl and methylene groups in coal at high temperatures were analyzed by Fourier transform infrared spectroscopy. Elemental mapping by energy dispersive X-ray spectroscopy indicated that the inorganic silica gel blends uniformly with the polymeric gel. Fire extinction experiments indicated that the HPAM-Al3+/WG gel reduces the fire-source temperature, heat radiation, and CO generation. Thus, the HPAM-Al3+/WG gel is an ideal fire prevention and extinction material.