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Magnetic resonance imaging (MRI) is recognized as the most powerful clinical imaging modality due to its ability to generate detailed three-dimensional anatomical images with high ...spatial resolution in a non-invasive manner without requiring harmful ionizing radiation. Conventionally, exogenous paramagnetic transition metal ion chelates or iron oxide nanoparticles are used as contrast agents (CAs) to enhance the image contrast of anatomical features. However, despite the wide use of these metal-based CAs, safety concerns have been raised regarding their potential toxic effects resulting from long-term in vivo accumulation. This has driven the development of organic metal-free CAs in various forms for use in MRI. Importantly, functional polymers capable of MRI via different mechanisms represent one of the most promising alternatives to current metal-based MRI CAs due to appealing features such as low toxicity, improved pharmacokinetics and biodistribution profile, and tailored structures and functionalities. Such structural and functional flexibility can enable a myriad of biomedical applications. In this review, we will highlight advances in the development of functional polymers as organic metal-free macromolecular MRI CAs based on different mechanisms including polymeric nitroxide-based 1H MRI CAs, polymeric chemical exchange saturation transfer (CEST) MRI CAs, and polymeric heteronuclei-based MRI CAs. In addition, the review will address the challenges and future opportunities for these promising classes of metal-free polymeric MRI CAs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
CD8+ exhausted T cells (Tex) are heterogeneous. PD-1 inhibitors reinvigorate progenitor Tex, which subsequently differentiate into irresponsive terminal Tex. The ability to maintain a capacity for ...durable proliferation of progenitor Tex is important, but the mechanism remains unclear. Here, we showed CD8+ progenitor Tex pretreated with decitabine, a low-dose DNA demethylating agent, had enhanced proliferation and effector function against tumors after anti-PD-1 treatment in vitro. Treatment with decitabine plus anti-PD-1 promoted the activation and expansion of tumor-infiltrated CD8+ progenitor Tex and efficiently suppressed tumor growth in multiple tumor models. Transcriptional and epigenetic profiling of tumor-infiltrated T cells demonstrated that the combination of decitabine plus anti-PD-1 markedly elevated the clonal expansion and cytolytic activity of progenitor Tex compared with anti-PD-1 monotherapy and restrained CD8+ T cell terminal differentiation. Strikingly, decitabine plus anti-PD-1 sustained the expression and activity of the AP-1 transcription factor JunD, which was reduced following PD-1 blockade therapy. Downregulation of JunD repressed T cell proliferation, and activation of JNK/AP-1 signaling in CD8+ T cells enhanced the antitumor capacity of PD-1 inhibitors. Together, epigenetic agents remodel CD8+ progenitor Tex populations and improve responsiveness to anti-PD-1 therapy.
Prometryne is a widely used herbicide in China to control annual grasses and broadleaf weeds. However, the stability of prometryne makes it difficult to be degraded, which poses a threat to human ...health. This study presents a bacterial strain isolated from soil samples with a prometryne application history, designated strain DY-1. Strain DY-1, identified as
Pseudomonas
sp., is capable of utilizing prometryne as a sole carbon source for growth and degrading 100% of prometryne within 48 h from an initial concentration of 50 mg L
−1
. To further optimize the degradation of prometryne, the prometryne concentration, temperature, pH, and salt concentration were examined. The optimal conditions for degradation of prometryne by strain DY-1 were an initial prometryne concentration of 50 mg L
−1
, 30 °C, pH 7–8, and NaCl concentration of 200 mg L
−1
. The same strain also degraded other s-triazine herbicides, including simetryne, ametryne, desmetryne, and metribuzin, under the same conditions. The biodegradation pathway of prometryne was established by isolating sulfoxide prometryne as the first metabolite and by the identification of sulfone prometryne and 2-hydroxy prometryne by liquid chromatography-mass spectrometry (LC–MS/MS). The results illustrated that strain DY-1 achieved the removal of prometryne by gradually oxidizing and hydrolyzing the methylthio groups. A bioremediation trial with contaminated soil and pot experiments showed that after treating the prometryne-contaminated soil with strain DY-1, the content of prometryne was significantly reduced (
P
< 0.05). This study provides an efficient bacterial strain and approach that could be potentially useful for detoxification and bioremediation of prometryne analogs.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Rating predictions, as an application that is widely used in recommender systems, have gradually become a valuable way which can help user narrow down their choices quickly and make wise decisions ...from the vast amount of information. However, most existing collaborative recommendation models suffer from poor accuracy due to data sparsity and cold start problems that recommender systems contain only a few explicit data. To solve this problem, a new implicit trust recommendation approach (ITRA) is proposed to generate item rating prediction by mining and utilizing user implicit information in recommender systems. Specifically, user trust neighbor set that has similar preference and taste with a target user is first obtained by trust expansion strategy via user trust diffusion features in a trust network. Then, the trust ratings mined from user trust neighbors are used to compute trust similarity among users based on user collaborative filtering model. Finally, using the above filtered trust ratings and user trust similarity, the prediction results are generated by a trust weighting method. In addition, the empirical experiments are conducted on three real-world datasets, and the results demonstrate that our rating prediction model has obvious advantages over the state-of-the-art comparison methods in terms of the accuracy of recommendations.
Abstract
Sensitivity to platinum-based combination chemotherapy is associated with a favorable prognosis in patients with non-small cell lung cancer (NSCLC). Here, our results obtained from analyses ...of the Gene Expression Omnibus database of NSCLC patients showed that cartilage acidic protein 1 (CRTAC1) plays a role in the response to platinum-based chemotherapy. Overexpression of CRTAC1 increased sensitivity to cisplatin in vitro, whereas knockdown of CRTAC1 decreased chemosensitivity of NSCLC cells. In vivo mouse experiments showed that CRTAC1 overexpression increased the antitumor effects of cisplatin. CRTAC1 overexpression promoted NFAT transcriptional activation by increasing intracellular Ca
2+
levels, thereby inducing its regulated STUB1 mRNA transcription and protein expression, accelerating Akt1 protein degradation and, in turn, enhancing cisplatin-induced apoptosis. Taken together, the present results indicate that CRTAC1 overexpression increases the chemosensitivity of NSCLC to cisplatin treatment by inducing Ca
2+
-dependent Akt1 degradation and apoptosis, suggesting the potential of CRTAC1 as a biomarker for predicting cisplatin chemosensitivity. Our results further reveal that modulating the expression of CRTAC1 could be a new strategy for increasing the efficacy of cisplatin in chemotherapy of NSCLC patients.
Background
MicroRNAs (miRNAs), the key regulator of gene expression, and N6‐methyladenosine (m6A) RNA modification play a significant role in tumour progression. However, regulation of m6A‐modified ...mRNAs by miRNAs in colorectal cancer (CRC), and its effect on progression of CRC, remains to be investigated.
Methods
Expression of miR‐6125 and YTH Domain‐Containing Family Protein 2 (YTHDF2) was detected by western blotting and immunohistochemistry. The effects of miR‐6125 and YTHDF2 on proliferative capacity of CRC cells were analysed using soft agar, ATP, CCK8 and EdU assays, and in animal experiments.
Results
MiR‐6125 expression was downregulated markedly in CRC, and expression correlated negatively with tumour size and prognosis. MiR‐6125 targeted the 3′‐UTR of YTHDF2 and downregulated the YTHDF2 protein, thereby increasing the stability of m6A‐modified glycogen synthase kinase 3 beta (GSK3β) mRNA. Increased GSK3β protein levels inhibited the expression of Wnt/β‐catenin/Cyclin D1 pathway‐related proteins, leading to G0‐G1 phase arrest and ultimately inhibiting the proliferation of CRC cells.
Conclusions
MiR‐6125 regulates YTHDF2 and thus plays a critical role in regulating the Wnt/β‐catenin pathway, thereby affecting the growth of CRC. Collectively, these results suggest that miR‐6125 and YTHDF2 are potential targets for treatment of CRC.
MiR‐6125 regulates YTHDF2 and thus plays a key role in regulating the Wnt/β‐catenin pathway, thereby affecting growth of CRC both in vitro and in vivo. The results suggest that miR‐6125 and YTHDF2 are potential targets for treatment of CRC.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Transcribed ultraconserved regions (T-UCRs) are a new type of long non-coding RNA, and the UCR has 481 segments longer than 200 base pairs that are 100% conserved between humans, rats, and mice. ...T-UCRs involved in colorectal cancer (CRC) have not been studied in detail. We performed T-UCR microarray analysis and found that uc.77- was significantly downregulated in CRC tissues and cell lines. Ectopic expression of uc.77- significantly inhibited the proliferation of CRC cells
in vitro
and the growth of xenograft tumors in nude mice
in vivo
. Mechanistic studies showed that uc.77- competed with FBXW8 mRNA for binding to microRNA (miR)-4676-5p through a competing endogenous RNA mechanism and inhibited the proliferation of CRC cells by negatively regulating CDK4. The present findings highlight the role of the uc.77-/miR-4676-5p/FBXW8 axis in CRC and identify uc.77- as a potential novel target for the treatment of CRC.
In this paper, we proposed a contrast-enhanced homemade spectral domain optical coherence tomography (SD-OCT) method for monitoring of brain microcirculation. We used the polyethylene glycol ...(PEG)-ylated gold nanorods (GNRs) as a contrast-enhanced agent, obtained clearly 2D and 3D OCT images of blood vessels and dynamic changes of probes in mouse blood vessels. Owing to high scattering of the PEG-GNRs, more tiny blood vessels can be imaged and the OCT signal can be enhanced by 5.87 dB after injection of PEG-GNRs for 20
min, the enhancement then declined gradually for 60
min. Our results demonstrate an effective technique for the enhanced imaging of blood vessels in vivo, especially for studies of the brain microcirculation, which could be serviced for disease mechanism research and therapeutic drug monitoring.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Online recommender systems generally suffer from severe data sparsity problems, and this are particularly prevalent in newly launched systems that do not have sufficient amounts of data. Cross-domain ...recommendations can provide us with some new ideas for assisting with user recommendations in sparse target domains by transferring knowledge from a source domain with rich data. In this paper, a deep sparse autoencoder prediction model based on adversarial learning for cross-domain recommendations (DSAP-AL) is proposed to improve the accuracy of rating predictions in similar cross-domain recommender systems. Specifically, joint matrix factorization and adversarial network learning models are adopted to integrate and align user and item latent factor spaces in a unified pattern. Then, a deep sparse autoencoder is represented and modeled by transferring the latent factors and interlayer weights. Furthermore, a domain factor adaptation algorithm is proposed to capture robust user and item factors, and the learned regularization constraints are added to the objective function, thereby alleviating the data sparsity issue. Experimental results on four real-world datasets demonstrate that, even without overlapping entities (users or items) in the source and target domains, the proposed DSAP-AL method achieves competitive performance relative to other state-of-the-art individual and cross domain approaches. Moreover, the DSAP-AL model is not only effective for scenarios with sparse data but also robust for noise-containing recommendations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Responsive polymeric nanoparticles have been extensively studied for various biological applications to provide enhanced function accuracy. Here, we report the synthesis of oxidation-responsive ...polymeric fluorinated nanoparticles (FNPs) via a photopolymerization-induced self-assembly (photo-PISA) method using a thioether- and fluorine-containing monomer N-(2-((2,2,2-trifluoroethyl)thio)ethyl)acrylamide (FTAM) and a methoxy polyethylene glycol (mPEG)-based macro chain transfer agent. With the polymerization of FTAM, the resultant block copolymer mPEG-b-PFTAM undergoes spontaneous self-assembly into spherical nanoparticles, driven by the solvophobic nature of the PFTAM block. The mobility of fluorine spins is highly restricted in the nanoparticles, leading to diminished 19F nuclear magnetic resonance (NMR)/magnetic resonance imaging (MRI) signals. However, when the nanoparticles are exposed to oxidants, the hydrophobic thioether groups of PFTAM can be oxidized into hydrophilic sulfoxide groups. This transition can lead to the disassembly of the PISA nanoparticles and switching on of the 19F NMR/MRI signals, owing to increased mobility of the fluorinated segments. This oxidation-responsive capability makes these polymeric FNPs useful for applications associated with oxidative conditions.
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IJS, KILJ, NUK, PNG, UL, UM
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