Extreme hypoxia of tumors represents the most notable barrier against the advance of tumor treatments. Inspired by the biological nature of red blood cells (RBCs) as the primary oxygen supplier in ...mammals, an aggressive man‐made RBC (AmmRBC) is created to combat the hypoxia‐mediated resistance of tumors to photodynamic therapy (PDT). Specifically, the complex formed between hemoglobin and enzyme‐mimicking polydopamine, and polydopamine‐carried photosensitizer is encapsulated inside the biovesicle that is engineered from the recombined RBC membranes. The mean corpuscular hemoglobin of AmmRBCs reaches about tenfold as high as that of natural RBCs. Owing to the same origin of outer membranes, AmmRBCs share excellent biocompatibility with parent RBCs. The introduced polydopamine plays the role of the antioxidative enzymes existing inside RBCs to effectively prevent the oxygen‐carrying hemoglobin from the oxidation damage during the circulation. This biomimetic engineering can accumulate in tumors, permit in situ efficient oxygen supply, and impose strong PDT efficacy toward the extremely hypoxic tumor with complete tumor elimination. The man‐made pseudo‐RBC shows potentials as a universal oxygen‐self‐supplied platform to sensitize hypoxia‐limited tumor treatment means, including but not limited to PDT. Meanwhile, this study offers ideas to the production of artificial substitutes of packed RBCs for clinical blood transfusion.
Aggressive man‐made pseudo‐red blood cells (AmmRBCs) are prepared for self‐oxygen‐supplied photodynamic therapy (PDT) toward tumors. AmmRBCs can accumulate in tumors and exhibit high efficacy to combat hypoxia‐induced resistance of tumors to PDT, leading to complete tumor elimination.
Circular RNAs (circRNAs) have been reported to have critical regulatory roles in tumor biology. However, their contribution to melanoma remains largely unknown.
CircRNAs derived from oncogene CD151 ...were detected and verified by analyzing a large number of melanoma samples through quantitative real-time polymerase chain reaction (qRT-PCR). Melanoma cells were stably transfected with lentiviruses using circ_0020710 interference or overexpression plasmid, and then CCK-8, colony formation, wound healing, transwell invasion assays, and mouse xenograft models were employed to assess the potential role of circ_0020710. RNA immunoprecipitation, luciferase reporter assay and fluorescence in situ hybridization were used to evaluate the underlying mechanism of circ_0020710.
Our findings indicated that circ_0020710 was generally overexpressed in melanoma tissues, and high level of circ_0020710 was positively correlated with malignant phenotype and poor prognosis of melanoma patients. Elevated circ_0020710 promoted melanoma cell proliferation, migration and invasion in vitro as well as tumor growth in vivo. Mechanistically, we found that high level of circ_0020710 could upregulate the CXCL12 expression via sponging miR-370-3p. CXCL12 downregulation could reverse the malignant behavior of melanoma cells conferred by circ_0020710 over expression. Moreover, we also found that elevated circ_0020710 was correlated with cytotoxic lymphocyte exhaustion, and a combination of AMD3100 (the CXCL12/CXCR4 axis inhibitor) and anti-PD-1 significantly attenuated tumor growth.
Elevated circ_0020710 drives tumor progression via the miR-370-3p/CXCL12 axis, and circ_0020710 is a potential target for melanoma treatment.
Metastasis causes the vast majority of colorectal carcinoma (CRC)-related deaths. However, little is known about the specific traits and underlying mechanisms of metastasis-initiating cells in ...primary CRC. And whether or not circular RNAs (circRNAs) take part in this particular event remain not adequately stated yet.
A screening method based on Transwell assay was first applied to build CRC subgroups with different metastatic potential. High throughput RNA sequencing was used to find out novel metastatic drivers in CRC metastasis-initiating step. A series of in vitro and in vivo assays were further applied to elucidate the functions and underlying molecular mechanisms of circRNAs in CRC metastasis.
A circRNA consisting of exon 8-11 of LONP2, termed as circLONP2, was upregulated in metastasis-initiating CRC subgroups. Aberrant higher expression of circLONP2 was observed in primary CRC tissues with established metastasis, and along the invasive margin in metastatic site. High expression of circLONP2 predicted unfavorable overall survival. Functional studies revealed that circLONP2 could enhance the invasiveness of CRC cells in vitro, and targeting circLONP2 through anti-sense oligonucleotide (ASO) dramatically reduced the penetrance of metastasis to foreign organs in vivo. Mechanically, circLONP2 directly interacted with and promoted the processing of primary microRNA-17 (pri-miR-17), through recruiting DiGeorge syndrome critical region gene 8 (DGCR8) and Drosha complex in DDX1-dependent manner. Meanwhile, upregulated mature miR-17-5p could be assembled into exosomes and internalized by neighboring cells to enhance their aggressiveness.
Our data indicate that circLONP2 acts as key metastasis-initiating molecule during CRC progression through modulating the intracellular maturation and intercellular transfer of miR-17, resulting in dissemination of metastasis-initiating ability in primary site and acceleration of metastasis formation in foreign organs. circLONP2 could serve as an effective prognostic predictor and/or novel anti-metastasis therapeutic target in CRC treatment.
Kidney, bladder, and prostate cancer are the three major tumor types of the urologic system that seriously threaten human health. Circular RNAs (CircRNAs), special non-coding RNAs with a stabile ...structure and a unique back-splicing loop-forming ability, have received recent scientific attention. CircRNAs are widely distributed within the body, with important biologic functions such as sponges for microRNAs, as RNA binding proteins, and as templates for regulation of transcription and protein translation. The abnormal expression of circRNAs in vivo is significantly associated with the development of urologic tumors. CircRNAs have now emerged as potential biomarkers for the diagnosis and prognosis of urologic tumors, as well as targets for the development of new therapies. Although we have gained a better understanding of circRNA, there are still many questions to be answered. In this review, we summarize the properties of circRNAs and detail their function, focusing on the effects of circRNA on proliferation, metastasis, apoptosis, metabolism, and drug resistance in kidney, bladder, and prostate cancers.
The graft‐through synthesis of Janus graft block copolymers (GBCPs) from branched macromonomers composed of various combinations of homopolymers is presented. Self‐assembly of GBCPs resulted in ...ordered nanostructures with ultra‐small domain sizes down to 2.8 nm (half‐pitch). The grafted architecture introduces an additional parameter, the backbone length, which enables control over the thermomechanical properties and processability of the GBCPs independently of their self‐assembled nanostructures. The simple synthetic route to GBCPs and the possibility of using a variety of polymer combinations contribute to the universality of this technique.
Independently tunable polymer properties: Janus graft block copolymers were synthesized with different backbone length, which serves as a handle for tuning of the thermomechanical properties of the polymer. Simultaneously, the size of the ultra‐small nanodomains is controlled by the side chain length. A broad range of monomers can be used.
Circular RNAs (circRNAs), a novel class of noncoding RNAs, have recently drawn lots of attention in the pathogenesis of human cancers. However, the role of circRNAs in cancer cells ...epithelial-mesenchymal transition (EMT) remains unclear. In this study, we aimed to identify novel circRNAs that regulate urothelial carcinoma of the bladder (UCB) cells' EMT and explored their regulatory mechanisms and clinical significance in UCBs.
We first screened circRNA expression profiles using a circRNA microarray in paired UCB and normal tissues, and then studied the clinical significance of an upregulated circRNA, circPRMT5, in a large cohort of patients with UCB. We further investigated the functions and underlying mechanisms of circPRMT5 in UCB cells' EMT. Moreover, we evaluated the regulation effect of circPRMT5 on miR-30c, and its target genes,
and
, in two independent cohorts from our institute and The Cancer Genome Atlas (TCGA).
We demonstrated that upregulated expression of circPRMT5 was positively associated with advanced clinical stage and worse survival in patients with UCB. We further revealed that circPRMT5 promoted UCB cell's EMT via sponging miR-30c. Clinical analysis from two independent UCB cohorts showed that the circPRMT5/miR-30c/SNAIL1/E-cadherin pathway was essential in supporting UCB progression. Importantly, we identified that circPRMT5 was upregulated in serum and urine exosomes from patients with UCB, and significantly correlated with tumor metastasis.
CircPRMT5 exerts critical roles in promoting UCB cells' EMT and/or aggressiveness and is a prognostic biomarker of the disease, suggesting that circPRMT5 may serve as an exploitable therapeutic target for patients with UCB.
With WC as the reinforcing phase particles, the Fe-WC composite coatings with mass fractions 0–60 wt% of WC were fabricated on a 15CrNiMo cone bit steel by laser cladding. The phase composition, ...microstructure, microhardness, friction and wear properties of the composite coatings were studied. Moreover, special attention was paid to investigate the thermal damage forms of WC particles and its influence mechanism on the structure evolution and wear properties. The research results reveal that most of the WC particles maintain their complete morphology, but some WC particles are melted due to the thermal damage type of dissolution-collapse-precipitation. The degree of burning loss rate is related to the quantity distribution and average particle size of WC in local area. Main surrounding structures of WC are composed of equiaxed and cellular crystals, and few short columnar crystals. The microhardness of the WC-Fe composite coating increases with increasing WC particles content. Compared with the microhardness (621.7HV0.2) of the Fe-based coating, the microhardness of the WC-Fe composite coating gradually increased from 729.9HV0.2 to 1029.2HV0.2, and its average relative wear resistance is 1.3 times that of the coating without WC particles. Moreover, combined with existing WC and W2C, as well as the presence of precipitated M23C6, M7C3 and η phases, which significantly improve the wear resistance of WC-Fe composite coatings. In summary, the main wear mechanisms of Fe-based coatings reinforced by WC particles are abrasive wear accompanied by varying degrees of adhesive wear and three-body abrasive wear.
•Wear resistance, Phase composition, Microhardness of WC particle reinforced Fe based coating were discussed.•The evaluation method of WC particles burning degree was supplemented.•The effect of WC particles on the microstructure of Fe based coating was studied.
Abstract
Background
N6-methyladenosine (m6A) related long noncoding RNAs (lncRNAs) may have prognostic value in bladder cancer for their key role in tumorigenesis and innate immunity.
Methods
Bladder ...cancer transcriptome data and the corresponding clinical data were acquired from the Cancer Genome Atlas (TCGA) database. The m6A-immune-related lncRNAs were identified using univariate Cox regression analysis and Pearson correlation analysis. A risk model was established using least absolute shrinkage and selection operator (LASSO) Cox regression analyses, and analyzed using nomogram, time-dependent receiver operating characteristics (ROC) and Kaplan–Meier survival analysis. The differences in infiltration scores, clinical features, and sensitivity to Talazoparib of various immune cells between low- and high-risk groups were investigated.
Results
Totally 618 m6A-immune-related lncRNAs and 490 immune-related lncRNAs were identified from TCGA, and 47 lncRNAs of their intersection demonstrated prognostic values. A risk model with 11 lncRNAs was established by Lasso Cox regression, and can predict the prognosis of bladder cancer patients as demonstrated by time-dependent ROC and Kaplan–Meier analysis. Significant correlations were determined between risk score and tumor malignancy or immune cell infiltration. Meanwhile, significant differences were observed in tumor mutation burden and stemness-score between the low-risk group and high-risk group. Moreover, high-risk group patients were more responsive to Talazoparib.
Conclusions
An m6A-immune-related lncRNA risk model was established in this study, which can be applied to predict prognosis, immune landscape and chemotherapeutic response in bladder cancer.
The design of smart stimuli‐responsive photoluminescent materials capable of multi‐level encryption and complex information storage is highly sought after in the current information era. Here, a ...novel adamantyl‐capped CsPbBr3 (AD‐CsPbBr3) perovskite NCs, along with its supramolecular host‐guest assembly partner a modified β‐CD (mCD), mCD@AD‐CsPbBr3, are designed and prepared. By dispersing these two materials in different solvents, namely, AD‐CsPbBr3 in toluene, mCD@AD‐CsPbBr3 in toluene, and mCD@AD‐CsPbBr3 in methanol, the three solutions exhibit diverse photoluminescence (PL) turn‐on/off or PL discoloration response upon supramolecular stimulus. Based on these responses, a proof‐of‐principle programmable Multi‐Level Photoluminescence Encoding System (MPLES) is established. Three types of four‐level and three types of three‐level information encoding are achieved by the system. A layer‐by‐layer four‐level information encryption and decryption as well as a two‐level encrypted 3D code are successfully achieved.
Adamantyl‐capped AD‐CsPbBr3 perovskite nanorods and their cyclodextrin‐coated counterparts, mCD@AD‐CsPbBr3, display varied photoluminescent turn on/off or discoloration responses to four stimuli. This enables a sophisticated encoding system capable of multi‐level encryption and decryption, including intricate four‐layer encryption/decryption processes and a dual‐level 3D code.
A novel smart fluorescent polymer polyethyleneimine‐grafted pyrene (PGP) is developed by incorporating four stimuli‐triggers at molecular level. The triggers are amphiphilicity, supramolecular ...host–guest sites, pyrene fluorescence indicator, and reversible chelation sites. PGP exhibits smart deformation and shape‐dependent fluorescence in response to external stimuli. It can deform into three typical shapes with a characteristic fluorescence color, namely, spherical core–shell micelles of cyan‐green fluorescence, standard rectangular nanosheets of yellow fluorescence, and irregular branches of deep‐blue fluorescence. A quasi‐reversible deformation between the first two shapes can be dynamically manipulated. Moreover, driven by reversible coordination and the resulting intramolecular photoinduced electron transfer, PGP can be used as an aqueous fluorescence ink with erasable and recoverable properties. The fluorescent patterns printed by PGP ink on paper can be rapidly erased and recovered by simple spraying a sequence of Cu2+ and ethylene diamine tetraacetic acid aqueous solutions. This erase/recover transformation can be repeated multiple times on the same paper. The multiple stimulus responsiveness of PGP makes it have potential applications in nanorobots, sensing, information encryption, and anticounterfeiting.
A smart single‐fluorophore polymer polyethyleneimine‐grafted pyrene (PGP) incorporating four stimuli‐triggers: amphiphilicity, supramolecular host–guest sites, pyrene fluorescence indicator, and reversible chelation sites, exhibits deformation and shape‐dependent fluorescence in response to external stimuli. Besides, PGP driven by its reversible chelation capacity can be used as an advanced fluorescent ink with erasable and recoverable properties.
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