Triple Sensing Modes for Triggered ß-Galactosidase Activity Assays Based on Kaempferol-Deduced Silicon Nanoparticles and Biological Imaging of MCF-7 Breast Cancer Cells.

ß-Galactosidase (ß-Gala) is an essential biomarker enzyme for early detection of breast tumors and cellular senescence. Creating an accurate way to monitor ß-Gala activity is critical for biological research and early cancer detection. This work used fluorometric, colorimetric, and paper-based color sensing approaches to determine ß-Gala activity effectively. Via the sensing performance, the catalytic activity of ß-Gala resulted in silicon nanoparticles (SiNPs), fluorescent indicators obtained via a one-pot hydrothermal process. As a standard enzymatic hydrolysis product of the substrate, kaempferol 3-O-ß-d-galactopyranoside (KOßDG) caused the fluorometric signal to be attenuated on kaempferol-silicon nanoparticles (K-SiNPs). The sensing methods demonstrated a satisfactory linear response in sensing ß-Gala and a low detection limit. The findings showed the low limit of detection (LOD) as 0.00057 and 0.098 U/mL for fluorometric and colorimetric, respectively. The designed probe was then used to evaluate the catalytic activity of ß-Gala in yogurt and human serum, with recoveries ranging from 98.33 to 107.9%. The designed sensing approach was also applied to biological sample analysis. In contrast, breast cancer cells (MCF-7) were used as a model to test the in vitro toxicity and molecular fluorescence imaging potential of K-SiNPs. Hence, our fluorescent K-SiNPs can be used in the clinic to diagnose breast cellular carcinoma, since they can accurately measure the presence of invasive ductal carcinoma in serologic tests.

A novel "Turn-on" fluorometric assays triggered reaction for ß-glucosidase activity based on quercetin derived silicon nanoparticles and its potential use for cell imaging.

ß-Glucosidase (ß-Gluco) is an enzyme that is crucial to numerous diseases, including cancer, and in sector of industries, it is used in the manufacturing of food. Measuring its enzymatic activity is critical for biomedical studies and other activities. Herein, we have developed a novel and precise fluorescent sensing method for measuring ß-Gluco activity based on the production of yellow-green fluorescent quercetin-silicon nanoparticles (Q-SiNPs) produced from quercetin (QN) as a reducing agent and 3-[2-(2-aminoethyl amino) ethylamino] propyl-trimethoxy silane (AEEA) as a silane molecule. ß-Gluco hydrolyzed quercetin-3-O-ß-d-glucopyranoside (QO-ß-DG) to produce QN, which was then used to produce Q-SiNPs. Reaction parameters, including temperature, time, buffer, pH, and probe concentration, were carefully tuned in this study. Subsequently, the fluorescence intensity was performed, showing good linearity (R2 = 0.989), a broad linear dynamic range between 0.5 and 12 U L-1, and a limit of detection (LOD) as low as 0.428 U L-1, which was proven by fluorescence measurements. Most importantly, various parameters were detected and characterized with or without ß-Gluco. The designed probe was successively used to assess ß-Gluco activity in human serum and moldy bread. However, the mathematical findings revealed recoveries for human serum ranging from 99.3 to 101.66% and for moldy bread from 100.11 to 102.5%. Additionally, Q-SiNPs were well suited to being incubated in vitro with L929 and SiHa living cells, and after using an Olympus microscope, imaging showed good fluorescence cell images, and their viability evinced minimal cytotoxicity of 77% for L929 and 88% for SiHa. The developed fluorescence biosensor showed promise for general use in diagnostic tests. Therefore, due to this outstanding sensing modality, we anticipate that this research can provide a novel schematic project for creating simple nanostructures with a suitable plan and a green synthetic option for enzyme activity and cell imaging.

Azophenyl Calix[4]arene Porous Organic Polymer for Extraction and Analysis of Triphenylmethane Dyes from Seafood.

Porous organic polymers (POPs) based on calix[4]arene with a hydrophobic π-rich cavity and host-guest recognition properties exhibit a wide application range of molecular extraction and separation. However, it is still a challenge to improve the extraction and separation selectivity by exploring and seeking appropriate building blocks for the functionalization and pore size adjustment of calix[4]arene. Herein, an azophenyl calix[4]arene porous organic polymer (AC-POP) was proposed. By introducing an electron-rich cavity and adjusting the pore sizes of calix[4]arene, the AC-POP showed high selectivity extraction performance in triphenylmethane (TPM) dyes. The extraction mechanism was explored by adsorption thermodynamics study, density functional theory (DFT) calculation, and reduced density gradient (RDG) and electrostatic potential (ESP) analyses, which suggested that the selectivity adsorption of TPM dyes based on AC-POP was mainly the result of entropy driven by the hydrophobic effect. In addition, the noncovalent interactions including π-π stacking, van der Waals force, and electrostatic interaction were also important factors affecting the adsorption capacity of TPM dyes. Under optimal extraction conditions, the AC-POP possessed a maximum extraction amount of 95.3 mg·g-1 for Rhodamine B (RB), high enrichment factor of about 100, and excellent reusability more than 10 times. Then, an analytical method of TPM dyes with AC-POP as a solid-phase extractant combined with high-performance liquid chromatography-ultraviolet (HPLC-UV) was established, which displayed excellent sensitivity with the limits of detection (LODs) and limits of quantitation (LOQs) in the ranges of 0.004-0.35 and 0.016-1.16, respectively. The mean recoveries for TPM dyes ranged from 85.0 to 109.4% with an RSD of 0.48-9.45%. The proposed method was successfully applied to the analysis of the five TPM dyes in seafood matrix samples.

Rapid and Selective 19F NMR-Based Sensors for Fingerprint Identification of Ribose.

Ribose plays an important role in the process of life. Excessive ribose in the human cerebrospinal fluid or urine can be used as an early diagnostic marker of leukoencephalopathy. Fluorinated phenylboronic acid combined with 19F NMR spectroscopy was a powerful method for molecular recognition. However, phenylboronic acid-based sensors for selective detection of ribose are rarely reported in the literature. In this study, the rapid and highly selective recognition of ribose was studied by 19F NMR and 2-fluorophenylboric acid. It was found that 2-fluoro-phenylboric acid was an appropriate 19F NMR-based sensor molecule for the determination of ribose under physiological conditions with high selectivity and robust anti-interference ability. When 2-fluorophenylboric acid was used for the detection of ribose in human urine without any sample pretreatment, a limit of detection of 78 µM was obtained at room temperature under given 19F NMR experimental conditions (400 MHz, 512 scans, ca. 12 min), which can well meet the needs of practical application.

Noncovalent Dual-Locked Near-Infrared Fluorescent Probe for Precise Imaging of Tumor via Hypoxia/Glutathione Activation.

Stimulus-responsive fluorescent probes have broad applications in the early detection and treatment of tumors and thus promote the personalized treatment of tumors and improve patient survival. Among the repertoires of probes, dual-locked near-infrared (NIR) fluorescent probes are of great significance due to their improved specificity and multiplex detection in tumor imaging but remain to be explored. In this work, a facile noncovalent strategy for constructing dual-locked probes was proposed. A glutathione (GSH)-activatable single-locked probe CySS (first lock) was preloaded into a hypoxia-responsive molecular container CF3C4A (second lock) through a host-guest interaction to form the dual-locked probe CF3C4A-CySS. Under physiological conditions, CF3C4A-CySS binds strongly to avoid undesired leakage in normal tissues. We have proven that CF3C4A-CySS can be activated and "turn on" its NIR fluorescent signal under the dual key stimulation of hypoxia and GSH in the tumor microenvironment, which enables precise tumor imaging with enhanced accuracy and specificity. Both in vitro and in vivo results indicated the superiority of CF3C4A-CySS in tumor imaging. This work not only provides an effective tool for tumor imaging but also proposes a promising strategy for dual-locked imaging agent construction.

Noncovalent Theranostic Prodrug for Hypoxia-Activated Drug Delivery and Real-Time Tracking.

Real-time tracking of hypoxia-activated prodrugs (HAPs) delivery and the release process is of great significance for innovative medical treatments and drug development. Existing theranostic methods for HAPs activation imaging are based on the covalent approach, which suffered from complicated molecular design and tedious synthesis. In this work, a facile noncovalent strategy for constructing an hypoxia-activated theranostic prodrug has been proposed. An hypoxia-activated prodrug, NMAC4A, has been synthesized and bound with an NIR fluorophore CyNH2 through host-guest interaction to form the theranostic prodrug NMAC4A-CyNH2. Interestingly, the NIR fluorescence signal of CyNH2 can be effectively "turned off" after the formation of the stable theranostic prodrug NMAC4A-CyNH2. Because of the selective response to a tumor hypoxic microenvironment, NMAC4A-CyNH2 can realize the tumor-targeted drug delivery, accompanied by its NIR fluorescence "turn on". The synchronization of drug release and fluorescence "turn on" properties of NMAC4A-CyNH2 in an hypoxic microenvironment makes the fluorescence signal an effective tool for a precise tracing of the drug release process. Notably, NMAC4A-CyNH2 has been successfully applied to real-time image tracking of the drug delivery in vitro and in vivo. More importantly, the biodistribution of the theranostic prodrug's metabolites in a tumor and some major tissues have been mapped by mass spectrometry imaging at the molecular level, which further validated the effectiveness of NMAC4A-CyNH2 as a tumor-targeted drug delivery platform and NIR probe. This work will not only provide a promising tool for an hypoxia-activated drug delivery and real-time image tracking but also propose an effective design strategy for noncovalent theranostic prodrug construction.

Design and synthesis of novel 20(S)-α-aminophosphonate derivatives of camptothecin as potent antitumor agents.

29 novel 20(S)-aminophosphonate derivatives of camptothecin were synthesized via a FeCl3 - catalyzed one-pot reaction. All of these compounds displayed similar or superior cytotoxic activity in comparison with that of Irinotecan against Hep3B, MCF-7, A-549, MDA-MB-231, KB, and multidrug-resistant (MDR) KB-vin cell lines. Out of them, compound B07 exhibited significant cytotoxicity and 10-fold improvement in activity compared to Irinotecan. Mechanistically, B07 not only induced cell apoptosis and cell cycle arrest in Hep3B and MCF-7 cells, but also inhibited Topoisomerase I activity in the cell and cell-free system in a manner similar to that of Irinotecan. In both xenograft and primary HCC mouse models, B07 showed significant anti-tumor activity and was more potent than Irinotecan. Additionally, the acute toxicity assay showed that B07 had no apparent toxicity to the mouse liver, kidney, and hemopoietic system of the FVB/N mice. Therefore, these findings indicate that compound B07 could be a potential Topoisomerase I poison drug candidate for further clinical trial.

Spatial distribution analysis of phospholipids in rice by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry imaging.

Phospholipids are one of the main nutrients in rice, which have a positive effect on cancer, coronary heart disease and inflammation. However, phospholipids will become small molecular volatile substances during the aging process of rice, resulting in change the flavor of rice. Therefore, mapping the concentration and the spatial distribution of phospholipids in rice are of tremendous significance in its function research. In this work, we established a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) imaging method for the spatial distribution analysis of phospholipids in rice. A total of 12 phospholipid compounds were found in the range of m/z 500-1000 through a series of conditions optimization. According to the results, lysophosphatidylcholine (LPC) species spread throughout the rice tissue sections and phosphatidylcholine (PC) species distributed in the bran and embryo (particularly in the scutellum). We also compared the signal intensities of phospholipids in different parts of white rice and brown rice by region of interest (ROI) analysis, which showed the relative content of PC species was higher in the embryo and gradually decreased until disappeared with the increase of processing degree during the processing of brown rice to white rice. The PC species on the surface of rice could be used as an important indicator to identify the processing degree of rice. Our work not only establish a MALDI-TOF-MS imaging method for spatial distribution analysis of rice, but also provide the necessary reference for ensuring food security, improving the eating quality of rice and the health benefits of consumers.

A colon-targeted podophyllotoxin nanoprodrug: synthesis, characterization, and supramolecular hydrogel formation for the drug combination.

Making full use of the undeveloped bioactive natural product derivatives by selectively delivering them to target sites can effectively increase their druggability and reduce the wastage of resources. Azo-based prodrugs are widely regarded as an effective targeted delivery means for colon-related disease treatment. Herein, we report a new-type of azo-based nanoprodrug obtained from bioactive natural products, in which the readily available podophyllotoxin natural products are connected with methoxy polyethylene glycol (mPEG) via a multifunctional azobenzene group. The amphiphilic prodrug can form nanosized micelles in water and will be highly selectively activated by azoreductases, leading to the in situ generation of anticancer podophyllotoxin derivatives (AdP) in the colon after the cleavage of the azo bond. To satisfy the demand of drug carriers for cancer combination therapy in clinics, α-CD is further introduced into this nanoprodrug micelle system to form a supramolecular hydrogel via a cascade self-assembly strategy. Using imaging mass spectrometry (IMS), the colon-specific drug release ability of the hydrogel after oral administration is demonstrated at the molecular level. Finally, the nanoprodrug hydrogel is further used as a carrier to load a hydrophilic anti-cancer drug 5-FU during the hierarchical self-assembly process and to co-deliver AdP and 5-FU for the drug combination. The combination use of AdP and 5-FU provides enhanced cytotoxicity which indicates a significant synergistic interaction. This work offers a new way to enhance the therapeutic effect of nanoprodrugs via drug combination, and provides a new strategy for reusing bioactive natural products and their derivatives.

Reinforced Supramolecular Hydrogels from Attapulgite and Cyclodextrin Pseudopolyrotaxane for Sustained Intra-Articular Drug Delivery.

Injectable hydrogels for nonsteroidal anti-inflammatory drugs' (NSAIDs) delivery to minimize the side effects of NSAIDs and achieve long-term sustained release at the targeted site of synovial joint are attractive for osteoarthritis therapy, but how to improve its mechanical strength remains a challenge. In this work, a kind of 1D natural clay mineral material, attapulgite (ATP), is introduced to a classical cyclodextrin pseudopolyrotaxane (PPR) system to form a reinforced supramolecular hydrogel for sustained release of diclofenac sodium (DS) due to its rigid, rod-like morphology, and unique structure, which has great potential in tissue regeneration, repair, and engineering. Investigation on the interior morphology and rheological property of the obtained hydrogel points out that the ATP distributed in PPR hydrogel plays a role similar to the "reinforcement in concrete" and exhibits a positive effect on improving the mechanical properties of PPR hydrogel by regulating their interior morphology from a randomly distributed style to the well-ordered porous frame structure. The hybrid hydrogels demonstrate good shear-thinning and thixotropic properties, excellent biocompability, and sustained release behavior both in vitro and in vivo. Furthermore, preliminary in vivo treatment in an acute inflammatory rat model reveals that the ATP hybrid hydrogels present sustained anti-inflammatory effect.

Precisely Traceable Drug Delivery of Azoreductase-Responsive Prodrug for Colon Targeting via Multimodal Imaging.

We report the development of an azoreductase-responsive prodrug AP-N═N-Cy in which the precursor compound AP, a readily available podophyllotoxin derivative, is linked with a NIR fluorophore (Cy) via a multifunctional azobenzene group. This type of azo-based prodrug can serve as not only an azoreductase-responsive NIR probe to real-time tracking of the drug delivery process but also a delivery platform for an anticancer compound (AdP). We have shown that cleavage of the multifunctional azobenzene group in AP-N═N-Cy only occurred in the presence of azoreductase, which specifically secretes in the colon, resulting in direct release of AdP through an in situ modification of a phenylamino group on the precursor AP. Moreover, introduction of the azobenzene group endows the prodrug with an unique fluorescence "off-on" property and served as a switch to "turn on" the fluorescence of Cy as consequence of a self-elimination reaction with breakage of an azo bond. Such a prodrug can be administered orally and exhibit high stability and low toxicity before arriving at the colon. In view of the synchronism of drug release and the fluorescence turn-on process, the fluorescence imaging method was utilized to precisely trace drug delivery in vitro, ex vivo, and in vivo. Distinguishingly, the biodistribution of AdP and Cy in various tissues was further precisely mapped at the molecular level using imaging mass spectrometry. To the best of our knowledge, this is the first time that the in vivo real-time precise tracking of the colon-specific drug release and biodistribution was reported via a multimodal imaging method.

Design, synthesis and antineoplastic activity of novel 20(S)-acylthiourea derivatives of camptothecin.

For the purpose of advancing our research on diverse C-20 decorated derivatives of camptothecin (CPT), 46 new CPT acylthiourea derivatives were synthesized and evaluated in vitro for their cytotoxicity. All the compounds showed promising in vitro cytotoxicity against six tumor cell lines (Hep3B, MCF7, A549, MDA-MB-231, KB and KB-vin). Out of them, compound c20 possesses remarkable in vitro cytotoxic activity and is more potent than topotecan. Mechanistically, c20 not only induces cell cycle arrest and cell apoptosis in A549 cells, but also inhibits Topo I activity in the cell and cell-free system in a manner similar to that of topotecan. In both xenograft and primary HCC mouse models, c20 displays significant in vivo anti-cancer activity and is more potent than topotecan. In addition, the acute toxicity assay showed that c20 has no apparent toxicity to mouse liver, kidney and hemopoietic system of the FVB/N mice. Take together, these results indicated that compound c20 could be a potential anti-cancer candidate for further clinical trial.

A fluorescent molecularly imprinted device for the on-line analysis of AFP in human serum.

MIT is a promising strategy in antibody free analysis for tumour markers. Conventional nanosized MIPs with off-line analysis are beset by tedious operation and unsatisfactory analysis performance. In this work, an on-line analytical device to directly detect AFP, which is a typical tumour marker in cancer screening, was prepared for the first time. A microscope slide was chosen to be the basis of the device. APBA-PA, a polymerizable fluorescent boronic acid monomer, was synthesised and grafted on the surface of the microscope slide to act as the signal transduction pathway between the templates and the device. Along with the hydrolysis of TEOS and the elution of the templates, a portable, stable, easy to operate and low-cost analysis device for AFP with excellent repeatability was successfully prepared. Owing to the excellent selectivity and highly sensitive fluorescence response ability of the device towards the templates, the on-line detection of AFP in human serum was realized. A series of characterizations were applied to the device, and its analysis performance and possible detection mechanism were carefully studied. Furthermore, the device exhibited appropriate application prospects by comparing its analysis results with those of the commercially available ELISA. In our perception, this work is an important step towards MIPs for clinical applications.

Early Intratracheal Administration of Corticosteroid and Pulmonary Surfactant for Preventing Bronchopulmonary Dysplasia in Preterm Infants with Neonatal Respiratory Distress Syndrome: A Meta-analysis.

There is uncertain result with regard to the use of inhalation or instillation steroids to prevent bronchopulmonary dysplasia in preterm infants. This meta-analysis was designed to evaluate the efficacy and safety of early airway administration (within 2 days after birth) of corticosteroids and pulmonary surfactant (PS) for preventing bronchopulmonary dysplasia (BPD) in premature infants with neonatal respiratory distress syndrome (NRDS). The related studies were retrieved in PubMed, EMBASE, the Cochrane Library, Clinical Trial, CNKI, Wanfang and VIP Database from inception to August 2018. Two reviewers independently screened the studies to ensure that all patients with diagnosis of NRDS were enrolled to studies within 1 day after birth, assessed the quality of included studies by GRADEpro system and extracted the data for review. The meta-analysis was performed by RevMan 5.2 software. A subgroup analysis about inhaled corticosteroid (ICS) delivery method was made between ICS inhalation subgroup [inhalation of ICS by nebulizer or metered dose inhaler (MDI)] and ICS intratracheal instillation subgroup (PS used as a vehicle). Eight randomized controlled trials were enrolled in the meta-analysis, 5 trials of which stated the randomized method, grouping and blinded method, and the follow-up procedures were reported. GRADEpro system showed high quality of 4 trials (5 articles), and the rest 4 trials had moderate quality. Meta-analysis showed that the incidence of BPD was decreased in ICS group, the relative risk (RR) was 0.56 (95% CI: 0.42-0.76), and similar trends were found in ICS inhalation subgroup and ICS intratracheal instillation subgroup, with the corresponding RR being 0.58 (95% CI: 0.41-0.82) and 0.47 (95% CI: 0.24-0.95) respectively. ICS could also significantly reduce the mortality risk as compared with placebo control group (RR: 0.67; 95% CI: 0.45-0.99), with RR of ICS inhalation subgroup and ICS intratracheal instillation subgroup being 0.81 (95% CI: 0.34-1.94) and 0.64 (95% CI: 0.41-0.99) respectively. Moreover, the percentage of infants using PS more than one time was lower in ICS group than in the placebo control group, with the RR and 95% CI being 0.55 (95% CI: 0.45-0.67), and that in ICS intratracheal instillation subgroup lower than in ICS inhalation subgroup (RR: 0.56; 95% CI: 0.45-0.69, and RR: 0.35; 95% CI: 0.08-1.52 respectively). There was no significant difference in the incidence of infection or retinopathy of prematurity and neuro-motor system impairment between ICS group and placebo control group, with the corresponding RR being 0.95 (95% CI: 0.59-1.52), 0.92 (95% CI: 0.62-1.38) and 1.13 (95% CI: 0.92-1.39), respectively. It was concluded that early administration of ICS and PS is an effective and safe option for preterm infants with NRDS in preventing BPD and reducing mortality, decreasing the additional PS usage, especially for the ICS intratracheal instillation subgroup. Furthermore, the appropriate dose and duration of ICS, combined use of inhalation or instillation of ICS with PS and the long-term safety of airway administration of corticosteroids need to be assessed in large trials.

Design, Synthesis of N-phenethyl Cinnamide Derivatives and Their Biological Activities for the Treatment of Alzheimer's Disease: Antioxidant, Beta-amyloid Disaggregating and Rescue Effects on Memory Loss.

Gx-50 is a bioactive compound for the treatment of Alzheimer's disease (AD) found in Sichuan pepper (Zanthoxylum bungeanum). In order to find a stronger anti-AD lead compound, 20 gx-50 (1⁻20) analogs have been designed and synthesized, and their molecular structures were determined based on nuclear magnetic resonance (NMR) and mass spectrometry (MS) analysis, as well as comparison with literature data. Compounds 1⁻20 were evaluated for their anti-AD potential by using DPPH radical scavenging assay for considering their anti-oxidant activity, thioflavin T (ThT) fluorescence assay for considering the inhibitory or disaggregate potency of Aß, and transgenic Drosophila model assay for evaluating their rescue effect on memory loss. Finally, compound 13 was determined as a promising anti-AD candidate.

Prodrug-Based Cascade Self-Assembly Strategy for Precisely Controlled Combination Drug Therapy.

The development of codelivery systems for combination therapy that can load different drugs in a single carrier and precisely deliver payloads (ratio and administration time) via programmable administration has proven to be challenging. By taking advantage of the increased dimension or space from particle self-assembly approach, we have developed a prodrug-based cascade self-assembly strategy to construct a supramolecular hydrogel that can load different drugs in stages yet temporally/spatially release drugs by cascade disassembly of supramolecular hydrogel under different microenvironments. The cascade self-assembly mechanism has been investigated in detail by morphology evolution of prodrug micelles. Using tumor cell uptake, cytotoxicity assay, and a tumor-bearing animal model, the effectiveness of the prodrug micelle-based cascade self-assembly system was studied, such as loading, controlling the drug ratio, and the administration time for possible therapeutic applications. These studies fully demonstrate the proof of concept and open up an attractive new way to construct multidrug-loaded carriers for combination therapy.

Mitral valve repair using an autologous pericardial strip in infants and young children.

We have modified the mitral repair technique in infants and small children by using autologous pericardial strips to treat mitral regurgitation resulting from a dilated mitral annulus. Our results demonstrate that this technique maintains stability and flexibility of the mitral annulus and decreases the risk of mitral stenosis.

Diabetes mellitus and prognosis in women with breast cancer: A systematic review and meta-analysis.

BACKGROUND: Diabetes mellitus is associated with an increased risk of breast cancer, but studies of the effects of diabetes on the prognosis of women with breast cancer have yielded inconsistent findings. The present meta-analysis aimed to investigate the impact of preexisting diabetes on the prognosis in terms of overall survival (OS), disease-free survival (DFS), and relapse-free period (RFP) in women with breast cancer. METHODS: We searched the Embase and PubMed databases until June 2016 for cohort or case-control studies assessing the impact of diabetes on the prognosis of women with breast cancer. The pooled multivariate adjusted hazard ratio (HR) and their 95% confidence intervals (CIs) for OS, DFS, and RFP were used to analyze the impact of diabetes on the prognosis of breast cancer patients. RESULTS: Seventeen studies involving 48,315 women with breast cancer met our predefined inclusion criteria. Meta-analysis showed that the pooled adjusted HR was 1.51 (95% CI 1.34-1.70) for OS and 1.28 (95% CI 1.09-1.50) for DFS in breast cancer patients with diabetes compared to those without diabetes. However, RFP did not differ significantly between patients with and without diabetes (HR 1.42; 95% CI 0.90-2.23). CONCLUSIONS: The present meta-analysis suggests that preexisting diabetes is independently associated with poor OS and DFS in female breast cancer patients. However, the impact of diabetes on RFP should be further verified. More prospective studies are warranted to investigate whether appropriate glycemic control with modification of antihyperglycemic agents can improve the prognosis of female breast cancer patients with diabetes.

A three-dimensional graphene oxide supramolecular hydrogel for infrared light-responsive cascade release of two anticancer drugs.

A three dimensional supramolecular hydrogel consisting of prodrug-modified graphene oxide and α-cyclodextrin was developed. This hydrogel with a well-ordered interior microstructure integrated hydrophobic and hydrophilic anticancer drugs into a single multifunctional platform, and underwent a gel-sol transition leading to cascade release of two drugs in an on-demand fashion upon NIR light irradiation.

WITHDRAWN: LncRNA TUG1 promotes breast cancer cell proliferation via inhibiting miR-9.

Ahead of Print article withdrawn by publisher.