Synergistic Therapeutic Effects of D-Mannitol-Cerium-Quercetin (Rutin) Coordination Polymer Nanoparticles on Acute Lung Injury.

Acute lung injury (ALI) remains a significant global health issue, necessitating novel therapeutic interventions. In our latest study, we pioneered the use of D-mannitol-cerium-quercetin/rutin coordination polymer nanoparticles (MCQ/R NPs) as a potential treatment for ALI. The MCQ/R NPs, which integrate rutin and quercetin for their therapeutic potential and D-mannitol for its pulmonary targeting, displayed exceptional efficacy. By utilizing cerium ions for optimal nanoparticle assembly, the MCQ/R NPs demonstrated an average size of less than 160 nm. Impressively, these nanoparticles outperformed conventional treatments in both antioxidative capabilities and biocompatibility. Moreover, our in vivo studies on LPS-induced ALI mice showed a significant reduction in lung tissue inflammation. This groundbreaking research presents MCQ/R NPs as a promising new approach in ALI therapeutics.

A signal-switchable photoelectrochemical biosensor for ultrasensitive detection of long non-coding RNA in cancer cells.

Long non-coding RNA (LncRNA) as an emerging tumor biomarker plays a key factor in the early diagnosis of cancer. Herein, an innovative signal-switchable photoelectrochemical (PEC) biosensor based on ZrO2@CuO bimetallic oxides and T7 Exo-assisted signal amplification is reported for the ultrasensitive and selective detection of lncRNA (HOX gene antisense intergenic RNA, HOTAIR) in cancer cells. Firstly, MOFs-derived TiO2 nanodisks as an excellent photoactive material show an anodic background signal. When target lncRNA exists, the abundant auxiliary DNA1 is freed from T7 Exo-assisted cycle signal amplification, and then competitively hybridizes with auxiliary DNA2 on the electrode. Subsequently, bimetallic MOFs-derived ZrO2@CuO octahedra with a high specific surface area and porous structure are introduced into TiO2 nanodisks-modified biosensor, which appears a cathodic photocurrent and achieves a switchable signal. The developed signal-switchable PEC biosensor shows ultrasensitive detection of lncRNA HOTAIR with a detection limit of 0.12 fM, and can eliminate the false interference. Importantly, the established PEC biosensor has good correlation with RT-qPCR analysis (P < 0.05) for the quantification of lncRNA HOTAIR in cancer cells, which has great potential application for biomarker detection in the early diagnosis of cancer.

A dual-model immobilization-free photoelectrochemical/visual colorimetric bioanalysis based on microemulsion self-assemblies mediated multifunctional signal amplification strategy.

Herein, a novel silver ion-loaded gold microemulsion assemblies (Au/Ag+ MAs) mediated multifunctional signal amplification strategy was proposed to construct a sensitive immobilization-free photoelectrochemical (PEC)/colorimetric biosensor for carcinoembryonic antigen (CEA) detection. Through the sandwiched reaction among CEA, the CEA aptamer (DNA1) loaded on the Au nanoparticles (NPs) functionalized iron oxide (Fe3O4) nanospheres and another CEA aptamer (DNA2) immobilized on Au/Ag+ MAs, a complex is formed and acquired by magnetic separation. Then, Au/Ag+ MAs of the complex are disassembled into Au NPs and Ag+ ions driven by an acetone response, and the obtained demulsification solution is transferred to the cadmium sulfide/cadmium telluride (CdS/CdTe) photoactive composites modified electrode. Based on the multiple inhibition functions (blocking effect of oleylamine; energy transfer effect of Au NPs; and electron snatching effect of Ag+), the photocurrent of the electrode decreases obviously, resulting in the ultrasensitive detection of CEA (a detection limit of 16 fg mL-1). Interestingly, the ion-exchange reactions between CdS/CdTe composites and Ag+ ions generate silver sulfide/silver telluride (Ag2S/Ag2Te) composites, and a color change of composites can be distinguished directly, leading to a quick visual detection of CEA. Compared with the traditional single-modal assay for CEA, such dual-modal PEC/colorimetric assay is a more accurate and reliable due to different mechanisms and independent signal conversion. This work will offer a new perspective for the applications of various self-assemblies in PEC bioanalysis.

A Direct-Contact Photocurrent-Direction-Switching Biosensing Platform Based on In Situ Formation of CN QDs/TiO2 Nanodiscs and Double-Supported 3D DNA Walking Amplification.

Herein, a direct-contact photocurrent-direction-switching photoelectrochemical (PEC) biosensing platform for the ultrasensitive and selective detection of soluble CD146 (sCD146) is reported for the first time via in situ formation of carbon nitride quantum dots (CN QDs)/titanium dioxide (TiO2 ) nanodiscs with the double-supported 3D DNA walking amplification. In this platform, metal organic frameworks (MOFs)-derived porous TiO2 nanodiscs exhibit excellent anodic photocurrent, whereas a single-stranded auxiliary DNA (ssDNA) as biogate is absorbed onto the TiO2 nanodiscs to block active sites. Subsequently, with the help of intermediate DNAs from target sCD146-induced double-supported 3D DNA walking signal amplification, the ssDNA can leave away from the surface of TiO2 nanodiscs due to the specific hybridization with intermediate DNAs. Afterward, the successful direct contact of CN QDs on TiO2 nanodiscs by porosity and electrostatic adsorption, leads to the effective photocurrent-direction switching from anodic to cathodic photocurrent. Based on direct-contact photocurrent-direction-switching CN QDs/TiO2 nanodiscs system and double-supported 3D DNA walking signal amplification, sCD146 is detected sensitively with a wide linear range (10 fg mL-1 to 5 ng mL-1 ) and a low limit of detection (2.1 fg mL-1 ). Also, the environmentally friendly and direct-contact photocurrent-direction-switching PEC biosensor has an application prospect for cancer biomarker detection.

Fluorescent Sensor Based on Magnetic Separation and Strand Displacement Amplification for the Sensitive Detection of Ochratoxin A.

Ochratoxin A (OTA) is a common mycotoxin, and it is a significant threat to human health throughout the food chain. In this study, a sensitive and specific fluorescent sensor based on magnetic separation technology combined with chain displacement amplification was developed for fast and easy detection of OTA in food. The designed strand displacement amplification can improve the sensitivity for the detection, and the magnetic nanomaterials can provide a large surface area, thus enhancing the capture efficiency of the target from the sample. Based on those designs, the experimental results showed that the proposed method displayed excellent performance. The linearity range was 0.5-128.0 ng/mL. The detection limit was 0.125 ng/mL; the relative standard deviations were 3.92-7.71%. Additionally, the developed method was satisfactorily applied to determine OTA in wheat, corn, and red wine samples at three spiked levels (1.0, 8.0, and 64.0 ng/mL). The recoveries ranged from 85.45 to 107.8% for wheat flour, 101.34 to 108.35% for corn flour, and 91.15 to 93.80% for red wine, respectively. Compared with high-performance liquid chromatography, the proposed method showed a lower limit of detection and equal recovery. Hence, the designed method is a potential and good detecting tool for OTA residue analysis in complex matrix samples.

Fluorescence quenching determination of tetracyclines based on the synergistic oxidation effect between Fe3O4nanoparticles and tetracyclines.

In recent years, tetracyclines (TCs) is a hot research topic. Herein, we report an interesting discovery using the complexation of oxytetracycline and metal ions. In this study, according to the properties of Fe3O4nanoparticles (Fe3O4NPs) as a nanoenzyme, it can be used to catalyze the oxidation of KI by H2O2to produceI3-,while at the same timeI3-binds to rhodamine 6G (Rh6G) to form a conjoined particle (Rh6G ∼ I3)n, leading to a decrease in the fluorescence intensity of Rh6G. However, in the presence of TCs, Fe3O4NPs have a synergistic effect with TCs, leading to enhanced catalytic activity, as well as better selectivity compared to the activity of other reducing enzymes. Consequently,the fluorescent signal based on a resonance scattering effect between Rh6G andI3-is dependent on the concentration of TCs, thus achieving highly facile and robust detection of TCs. The limits of detection (LOD) of the method were 20 nM, 10 nM and 40 nM for oxytetracycline(OTC), tetracycline(TC) and chlortetracycline(CTC), respectively. Most importantly, the method can be successfully applied to the detection of TCs in milk, eggs, and honey. The recoveries of spiked samples ranged from 83.11 to 118.95%. Thus, a stable, hands-on strategy for the detection of TCs is proposed, which has potential applications in the field of food safety and environmental protection.

The mechanism of action of paeoniae radix rubra-angelicae sinensis radix drug pair in the treatment of rheumatoid arthritis through PI3K/AKT/NF-κB signaling pathway.

Objective: To investigate the effects and mechanisms of Paeoniae radix rubra-Angelicae sinensis radix (P-A) drug pair in the treatment of rheumatoid arthritis (RA). Methods: Mass spectrometry was employed to accurately characterize the main components of the P-A drug pair. Network pharmacology was used to analyze the main components and pathways of the P-A drug pair in the treatment of RA, and Discovery Studio software was used to molecularly dock the key proteins on the pathway with their corresponding compounds. The levels of serum TNF-a, IL-1ß, and IL-6 were measured by enzyme linked immunosorbent assay (ELISA). The histopathology of the ankle joint was observed by hematoxylin-eosin (HE) staining, and the positive expression of p-PI3K, p-IKK, p-NF-κB, and p-AKT in the synovial tissue of the ankle joint was detected by immunohistochemical analysis. Finally, the expression of PI3K, IKK, and AKT and their phosphorylation levels were determined by western blot in each group of rats. Results: Network pharmacology combined with molecular docking analysis revealed that the pharmacodynamic mechanism of the P-A drug pair for the treatment of RA may be related to the contents of caffeic acid, quercetin, paeoniflorin, and baicalein in the regulation of the expression of the PI3K/AKT/NF-κB signaling pathway and the targets of PIK3CA, PIK3R1, AKT1, HSP90AA1 and IKBKB in the pathway. Compared with the model group, the P-A drug pair significantly improved the pathological changes of the synovial tissue and reduced feet swelling in RA model rats. Moreover, it regulated the levels of TNF-α, IL-1ß, and IL-6 in serum (p < 0.05). The results of the immunohistochemical analysis and western blot showed that the expression of PI3K, IKK, NF-κB, and AKT decreased after phosphorylation in the synovial tissue (p < 0.05). Conclusion: The P-A drug pair exhibited an inhibitory effect on the hyperactivation of the PI3K/AKT/NF-κB signaling pathway in the synovial membrane of RA rats. The mechanism may be related to the downregulation of the phosphorylation levels PI3K, IKK, NF-κB, and AKT, which in turn decreased inflammatory cell infiltration and synovial membrane proliferation.

Magnetic-nanowaxberry-based microfluidic ExoSIC for affinity and continuous separation of circulating exosomes towards cancer diagnosis.

Exosomes are seen as promising biomarkers for minimally invasive liquid biopsies and disease surveillance. However, the complexity of body fluids, inherent heterogeneity, and tiny size of exosomes impede their extraction, consequently restricting their clinical application. In this study, in order to efficiently isolate exosomes from clinical samples, an irregular serpentine channel microfluidic chip (ExoSIC) was designed to continuously separate exosomes from plasma based on a magnetic-nanowaxberry (MNWB). In the ExoSIC, irregular serpentine microchannels are utilized to increase fluid chaotic mixing, hence improving exosome capture efficiency. In comparison to commonly used spherical magnetic particles, the designed MNWB can not only enhance the capture efficiency of exosomes, but also possess a size-exclusion effect to improve exosome purity. Consequently, the ExoSIC exhibited a large yield (24 times higher than differential centrifugation), optimum purity (greater than precipitation and similar to differential centrifugation), and high specificity. Furthermore, the ExoSIC was utilized for plasma-based cancer diagnosis by multiplex monitoring of five exosomal biomarkers (exosomal concentration, EGFR, EpCAM, SAA1 and FV), and the AUC reached 0.791. This work provides a comprehensive framework for exosome-based cancer diagnostics in order to meet clinical requirements for exosome isolation and downstream analysis.

Lycium barbarum polysaccharide protects cardiomyocytes from hypoxia/reoxygenation injury via activation of SIRT3/CypD signaling.

Background: Myocardial ischemia-reperfusion is a common pathological feature of many heart and vascular diseases, but the molecular mechanism of this process is still unclear, and there is no effective way to protect cardiomyocytes. The aim of this study was to examine the effects and underlying molecular mechanisms of Lycium barbarum polysaccharide (LBP) on myocardial ischemia-reperfusion injury in cardiomyocytes. Methods: The cardiomyocyte cell line H9c2 were used to establish an in vitro hypoxia/reoxygenation (H/R) model. After treatment with LBP and/or the SIRT3 inhibitor 3-TYP, cell morphology was observed under the light microscopy. The Cell Counting Kit (CCK)-8 and 5-ethynyl-2'-deoxyuridine (EdU) assay were used to detect cell proliferation, and flow cytometry was performed to assess cell apoptosis. The lysine (166)-acetylation of CypD1 was determined by co-immunoprecipitation assay. Enzyme-linked immunosorbent assay (ELISA) was used to determine the lactate dehydrogenase (LDH) level in the culture medium. Na+-K+-ATPase activity, Ca2+-ATPase activity, and nitric oxide (NO) levels were measured. Results: LBP alleviated cell damage and upregulated STIR3 expression in a dose-dependent manner. Upregulated SIRT3 expression and suppressed acetylation of CypD were also observed in H/R-induced H9c2 cells treated with LBP. Indeed, LBP remarkably reversed the inhibition of proliferation and cell apoptosis in H/R-induced H9c2 cells by activating SIRT3/CypD signaling. Blockade of SIRT3 with SIRT3 inhibitor (3-TYP) inhibited the protective effect of LBP on H9c2 cells. LBP markedly alleviated the H/R-induced increase of LDH release, and the decrease of Na+-K+-ATPase activity, Ca2+-ATPase activity, and NO levels. Inhibition of SIRT3 restored the protective effects of LBP. Conclusions: LPB induced deacetylation of CypD by upregulating SIRT3, thereby protecting mitochondrial function and relieving H/R-induced injury in cardiomyocytes.

Metabolomics study of ribavirin in the treatment of orthotopic lung cancer based on UPLC-Q-TOF/MS.

Ribavirin is a common antiviral drug, especially for patients with hepatitis C. Our recent studies demonstrated that ribavirin showed anti-tumor activity in colorectal cancer and hepatocellular carcinoma, but its effects on lung cancer remains unclear. This study aimed to evaluate the anti-tumor activity of ribavirin against lung cancer and elucidate the underlying mechanism. We established orthotopic mouse model of lung cancer (LLC and GLC-82) and employed an ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS)-based metabolomics approach. We found that ribavirin significantly inhibited the proliferation and colony formation of lung cancer cells. Tumor sizes of orthotopic lung cancer in ribavirin-treated groups were also significantly lower than those in control groups. Metabolomics analysis revealed that ribavirin mainly affected 5 metabolic pathways in orthotopic lung tumor models, taurine and hypotaurine metabolism, nicotinate and nicotinamide metabolism, linoleic acid metabolism, arginine biosynthesis and arachidonic acid metabolism. Furthermore, we identified 5 upregulated metabolites including ß-nicotinamide adenine dinucleotide (NAD+), nicotinamide (NAM), taurine, ornithine and citrulline, and 7 downregulated metabolites including 1-methylnicotinamide (MNAM), S-adenosyl-l-homocysteine (SAH), N1-Methyl-2-pyridone-5-carboxamide (2PY), homocysteine (Hcy), linoleic acid, arachidonic acid (AA) and argininosuccinic acid in ribavirin-treated groups. These results provide new insight into the anti-tumor mechanism of ribavirin for lung cancer.

Downregulation of PRMT5 by AMI-1 enhances therapeutic efficacy of compound kushen injection in lung carcinoma in vitro and in vivo.

Protein arginine methyltransferase 5 (PRMT5) is overexpressed in lung carcinoma, which promotes tumor cell proliferation, survival, migration and invasion. Compound Kushen injection (CKI) is a mixture of natural compounds extracted from Kushen and Baituling, which are mainly used to stop in cancer pain and bleeding. Here we found that cell viability and colony formation were inhibited after the incubation of AMI-1. Meanwhile, AMI-1 suppressed cell migration, enhanced apoptosis, induced cell cycle arrest, inhibited PRMT5 expression and histone H3R8 and H4R3 symmetric di-methylation (H3R8me2s and H4R3me2s) accumulation, down-regulated the expression of eukaryotic translation initiation factor 4E (eIF4E) in lung carcinoma cells. Moreover, AMI-1 suppressed tumor growth, decreased H3R8me2s and H4R3me2s accumulation, down-regulated eIF4E expression and increased p53 expression in lung carcinoma xenografts of BALB/c nude mice. Of note, combined and CKI markedly enhanced the anticancer efficacy CKI in lung carcinoma. The above findings demonstrated that AMI-1 has established antineoplastic activity and this role may be associated with affecting the function of eIF4E via inhibiting PRMT5 activity or protein levels in lung carcinoma. This study highlights evidence of novel selective anticancer activity of AMI-1 in combination with CKI in lung carcinoma.

Correction to "Fluorescent Sensor Based on Magnetic Separation and Strand Displacement Amplification for the Sensitive Detection of Ochratoxin A".

[This corrects the article DOI: 10.1021/acsomega.3c01408.].

Ribavirin inhibits cell proliferation and metastasis and prolongs survival in soft tissue sarcomas by downregulating both protein arginine methyltransferases 1 and 5.

Protein arginine methyltransferases 1 and 5 (PRMT1 and PRMT5) are frequently overexpressed in diverse types of cancers and correlate with poor prognosis, thus making these enzymes potential therapeutic targets. The aim of this study was to assess and elucidate the anti-tumour effect and epigenetic regulatory mechanism of ribavirin in soft tissue sarcomas (STS). We showed that ribavirin inhibited growth and metastasis and prolonged survival in animals bearing STS cells by downregulating the mRNA and protein levels of PRMT1/PRMT5 and attenuating the accumulation of asymmetric and symmetric di-methylation of arginine (ADMA and SDMA). Furthermore, ribavirin lowered the permeability of the peritoneum in KM mice bearing S180 ascites via decreasing the level of vascular endothelial growth factor (VEGF). Ribavirin was a potent inhibitor of cell proliferation and metastasis in STS cells through downregulation of both type I PRMT1 and type II PRMT5. Ribavirin could be used to enhance the efficacy of doxorubicin in STS allograft tumour models.

Ribavirin inhibits the growth and ascites formation of hepatocellular carcinoma through downregulation of type I CARM1 and type II PRMT5.

Type I co-activator-associated arginine methyltransferase 1 (CARM1) and type II protein arginine methyltransferase 5 (PRMT5) are highly expressed in multiple cancers including liver cancer and their overexpression contributes to poor prognosis, thus making them promising therapeutic targets. Here, we evaluated anti-tumor activity of ribavirin in hepatocellular carcinoma (HCC). We found that ribavirin significantly inhibited the proliferation of HCC cells in a time- and dose-dependent manner. Furthermore, ribavirin suppressed the growth of subcutaneous and orthotopic xenograft of HCC in mice, decreased vascular endothelial growth factor (VEGF) and peritoneal permeability to reduce ascites production, and prolonged the survival of mice in HCC ascites tumor models. Mechanistically, ribavirin potently down-regulated global protein expression of CARM1 and PRMT5, and concurrently decreased accumulation of H3R17me2a and H3R8me2s/H4R3me2s. However, ribavirin did not affect the activity and mRNA levels of both CARM1 and PRMT5 in vivo and in vitro HCC cells. In addition, our ChIP results shown that ribavirin inhibited CARM1 which in turn decreased the H3R17me2a, binds to the eukaryotic translation initiation factor 4E (eIF4E) and VEGF promoter region, and reduced the relative mRNA expression level of eIF4E and VEGF in HCC cells. Our findings suggested a potential therapeutic strategy for patients with HCC through inhibition of the abnormal activation/expression of both CARM1 and PRMT5.

Magnetic-Nanowaxberry-Based Simultaneous Detection of Exosome and Exosomal Proteins for the Intelligent Diagnosis of Cancer.

Exosome concentration and exosomal proteins are regarded as promising cancer biomarkers. Herein, a waxberry-like magnetic bead (magnetic-nanowaxberry) which has huge surface area and strong affinity was synthesized to couple with aptamer for exosome capture and recovery. Subsequently, we developed a fluorescent assay for the sensitive, accurate, and simultaneous quantification of exosome and cancer-related exosomal proteins [epidermal growth factor receptor (EGFR) and epithelial cell adhesion molecule (EpCAM)] by using triple-colored probes to recognize EGFR and EpCAM or spontaneously anchor to the lipid bilayer. In this design, the interference of soluble proteins can be avoided due to the dual recognition strategy. Moreover, the lipid-based quantification of exosome concentration can improve the accuracy. Besides, the simultaneous detection mode can save samples and simplify the operation steps. Consequently, the assay shows high sensitivity (the limits of detection are down to 0.96 pg/mL for EGFR, 0.19 pg/mL for EpCAM, and 2.4 × 104 particles/µL for exosome), high specificity, and satisfactory accuracy. More importantly, this technique is successfully used to analyze exosomes in plasma to distinguish cancer patients from healthy individuals. To improve the diagnostic efficacy, the deep learning was used to exploit the potential pattern hidden in data obtained by the proposed method. Also, the accuracy for the intelligent diagnosis of cancer can achieve 96.0%. This study provides a new avenue for developing new biosensors for exosome analysis and intelligent disease diagnosis.

A dual-model "on-super off" photoelectrochemical/ratiometric electrochemical biosensor for ultrasensitive and accurate detection of microRNA-224.

A dual-model "on-super off" photoelectrochemical (PEC)/ratiometric electrochemical (EC) biosensor based on signal enhancing and quenching combining three-dimensional (3D) DNA walker strategy was designed for the ultrasensitive and accurate detection of microRNA-224 (miRNA-224). The "signal on" PEC state was achieved by methylene blue labeled hairpin DNA (MB-DNA) for sensitizing CdS QDs. Then numerous transformational ferrocene labeled DNAs (Fc-DNAs) converted by target-induced 3D DNA walker amplification with the help of Ag nanocubes (NCs) label DNA (Ag-DNA) were introduced to open hairpin MB-DNA. Such configuration change would relocate the sensitizer MB and the quencher Fc, whereas energy transfer placed between Ag NCs and CdS QDs, thereby significantly quenching the PEC signal to obtain "super off" state. Meanwhile, these changes resulted in a decreased oxidation peak current of MB (IMB) and an increased that of Fc (IFc). MiRNA-224 was also detected on basis of the dual-signaling EC ratiometric method for complementary PEC detection. Benefiting from different mechanisms and relatively independent signal transduction, this approach not only avoided interference from difficult assembly but also outstandingly increased sensitivity by distance-controllable signal enhancing and quenching strategies. As a result, the detection ranges of 0.1-1000 fM with a low detection limit of 0.019 fM for PEC, and 0.52 to 500 fM with a low detection limit of 0.061 fM for EC, were obtained for miRNA-224, which opens a new avenue for designing numerous elegant biosensors with potential utility in bioanalysis and early disease diagnosis.

Plasmonic TiO2@Au NPs//CdS QDs photocurrent-direction switching system for ultrasensitive and selective photoelectrochemical biosensing with cathodic background signal.

An ultrasensitive and selective photoelectrochemical (PEC) biosensor with cathodic background signal was developed for the detection of carcinoembryonic antigen (CEA) based on innovative plasmonic TiO2@Au nanoparticles//CdS quantum dots (TiO2@Au NPs//CdS QDs) photocurrent-direction switching system, coupling with hybridization chain reaction (HCR) for the signal amplification. Firstly, innovative TiO2@Au NPs were successfully fabricated through in situ ascorbic acid-reduction of Au NPs dispersed on TiO2 surface, and TiO2@Au NPs as the photoactive material showed a cathodic background signal. When target CEA existed, a sandwich-type reaction was performed in capture CEA aptamer-modified TiO2@Au NPs and trigger CEA aptamer. Interestingly, after HCR triggered by target CEA, a mass of CdS QDs were introduced into the biosensing platform, resulting in the formation of TiO2@Au NPs//CdS QDs system, along with the switch of photocurrents from cathodic to anodic. The obtained remarkable anodic photocurrent was depended on the localized surface plasmon resonance (LSPR) effect of Au between TiO2 and CdS. Under the optimal conditions, plasmonic TiO2@Au NPs//CdS QDs photocurrent-direction switching PEC biosensing platform with cathodic background signal exhibited ultrasensitive for the determination of CEA with a low limit of detection of 18.9 fg/mL. Importantly, the proposed PEC biosensor can eliminate the interferences of the initial photocurrent and background signal, and has high-efficiency anti-interference ability, satisfactory stability and excellent reproducibility, which may have great potentials in bioanalysis and disease diagnosis.

2D metal-organic framework-based materials for electrocatalytic, photocatalytic and thermocatalytic applications.

Ultrathin two-dimensional metal-organic frameworks (2D MOFs) have recently attracted extensive interest in various catalytic fields (e.g., electrocatalysis, photocatalysis, thermocatalysis) due to their ultrathin thickness, large surface area, abundant accessible unsaturated active sites and tunable surface properties. Besides tuning the intrinsic properties of pristine 2D MOFs by changing the metal nodes and organic ligands, one of the hot research trends is to develop 2D MOF hybrids and 2D MOF-derived materials with higher stability and conductivity in order to further increase their activity and durability. Here, the synthesis of 2D MOF nanosheets is briefly summarized and discussed. More attention is focused on summaries and discussions about the applications of these 2D MOFs, their hybrids and their derived materials as electrocatalysts, photocatalysts and thermocatalysts. The superior properties and catalytic performance of these 2D MOF-based catalysts compared to their 3D MOF counterparts in electrocatalysis, photocatalysis and thermocatalysis are highlighted. The enhanced activities of 2D MOFs, their hybrids and derivatives come from abundant accessible active sites, a high density of unsaturated metal nodes, ultrathin thickness, and tunable microenvironments around the MOFs. Views regarding current and future challenges in the field, and new advances in science and technology to meet these challenges, are also presented. Finally, conclusions and outlooks in this field are provided.

Ribavirin inhibits colorectal cancer growth by downregulating PRMT5 expression and H3R8me2s and H4R3me2s accumulation.

Eukaryotic translation initiation factor 4E (eIF4E) and protein arginine methyltransferase 5 (PRMT5) are frequently overexpressed in colorectal cancer (CRC) tissues and associated with poor prognosis. Ribavirin, the only clinically approved drug known to target eIF4E, is an anti-viral molecule currently used in hepatitis C therapy. The potential of ribavirin to treat CRC remains largely unknown. Ribavirin treatment in CRC cell lines drastically inhibited cell proliferation and colony formation, induced S phase arrest and reduced cyclin D1, cyclin A/E and proliferating cell nuclear antigen (PCNA) levels in vitro, and suppressed tumorigenesis in mouse model of colitis-associated CRC. Mechanistically, ribavirin treatment significantly reduced PRMT5 and eIF4E protein levels and the accumulation of symmetric dimethylation of histone 3 at arginine 8 (H3R8me2s) and that of histone 4 at arginine 3 (H4R3me2s). Importantly, inhibition of PRMT5 by ribavirin resulted in promoted H3R8 methylation in eIF4E promoter region. Our results demonstrate the anti-cancer efficacy of ribavirin in CRC and suggest that the anti-cancer efficacy of ribavirin may be mediated by downregulating PRMT5 levels but not its enzymatic activity.